Acetosyringone （AS） has great influences on Agrobacterium-mediated genetic transformation. In order to improve the transformation frequency of waxy maize, in this study, shoot tips and immature embryo-derived callus...Acetosyringone （AS） has great influences on Agrobacterium-mediated genetic transformation. In order to improve the transformation frequency of waxy maize, in this study, shoot tips and immature embryo-derived callus of Lainongnuo 38 were collected as receptor materials, to compare the effects of pH in suspension medium, addition modes and concentrations of acetosyringone on genetic transformation of waxy maize. Results showed that adding 2 μl of 150 μmol/L AS in the wound with suspension medimn at pH 5.2 can significantly improve the transformation frequency of shoot tips of waxy maize; in genetic transformation of maize callus, adding 5 mg/L AS in infection solution can significantly improve the percentage of resistant callus.展开更多
Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuro...Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuropathy, and in vivo experimental data are lacking. We hypothesized that repeated applications of exogenous galanin over an extended time frame may also repair nerve damage in diabetic peripheral neuropathy, and relieve pain in vivo. We found that neuropathic pain occurred in streptozotocin-induced diabetic rats and was more severe after sciatic nerve pinch injury at 14 and 28 days than in diabetic sham-operated rats. Treatment with exogenous galanin alleviated the neuropathic pain and promoted sciatic nerve regeneration more effectively in diabetic rats than in non-diabetic rats after sciatic nerve pinch injury. This was accompanied by changes in the levels of endogenous galanin, and its receptors galanin receptor 1 and galanin receptor 2 in the dorsal root ganglia and the spinal dorsal horn when compared with nerve pinch normal rats. Our results show that application of exogenous galanin daily for 28 days can promote the regeneration of injured sciatic nerves, and alleviate neuropathic pain in diabetic rats.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for the...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for these reasons,it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment.The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled;consequently,at moment there are not effective treatments.In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis,to the vitamin D/vitamin D receptor(VD/VDR)axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD.However,the data currently available,including clinical trials with VD supplementation,still provides a contrasting picture.The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR.Based on recent data from literature,we focused in particular on the hypothesis that VDR itself,independently from its traditional ligand VD,may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.展开更多
The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pit...The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.展开更多
Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor...Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.展开更多
BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the ther...BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.展开更多
BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effec...BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.展开更多
Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsol...Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsolved issue in pain medicine.Our previous study,using protein kinase C gamma(PKCγ)-tdTomato mice,highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia.However,the regulatory mechanisms governing this circuit necessitate further elucidation.We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin(5-HT)facilitation system on spinal PKCγ neurons.Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_(2C) receptors,disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia.Inhibiting spinal 5-HT_(2C) receptors restored the feedforward inhibitory circuit,effectively preventing neuropathic allodynia.These insights offer promising therapeutic targets for neuropathic allodynia management,emphasizing the potential of spinal 5-HT_(2C) receptors as a novel avenue for intervention.展开更多
Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial ...Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.展开更多
Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown t...Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.展开更多
Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine a...Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.展开更多
Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to ins...Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to insomnia,in order to develop innovative therapies and new compounds.Recently,increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia.Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain.In this review,the role of 5-hydroxytryptamine(5-HT)in insomnia development is summarized,while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes,in order to provide reference for subsequent research.展开更多
Peroxisome-proliferator-activated receptors(PPARs) comprise three subtypes(PPARα,δ and γ) to form a nuclear receptor superfamily.PPARs act as key transcriptional regulators of lipid metabolism,mitochondrial biogene...Peroxisome-proliferator-activated receptors(PPARs) comprise three subtypes(PPARα,δ and γ) to form a nuclear receptor superfamily.PPARs act as key transcriptional regulators of lipid metabolism,mitochondrial biogenesis,and anti-oxidant defense.While their roles in regulating lipid metabolism have been well established,the role of PPARs in regulating redox activity remains incompletely understood.Since redox activity is an integral part of oxidative metabolism,it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state.The effects of PPAR signaling are directly related to PPAR expression,protein activities and PPAR interactions with their coregulators.The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue.Adding to the complexity,specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways.Moreover,the intensity and extension of redoxregulation by each PPAR subtype are varied depending on different tissues and cell types.Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups.The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms,as well as to discuss the implications in the cardiovascular system.展开更多
AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of ...AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.展开更多
The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors,which include epidermal growth factor receptor agonists and members of the transforming growth factor ...The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors,which include epidermal growth factor receptor agonists and members of the transforming growth factor β family.Furthermore,the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small,immunomodulatory proteins also play key roles in carcinogenesis and may,therefore,be potential targets for novel therapeutic approaches.In this review,we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.展开更多
AIM: To investigate the killing efficiency of a recombinant plasmid containing a thymidine kinase (TK) domain insert driven by the vascular endothelial growth factor receptor 2 (VEGFR2) promoter (KDR) on vascular endo...AIM: To investigate the killing efficiency of a recombinant plasmid containing a thymidine kinase (TK) domain insert driven by the vascular endothelial growth factor receptor 2 (VEGFR2) promoter (KDR) on vascular endothelial cells.METHODS: The KDR-TK fragment was extracted from pBluescript Ⅱ KDR-TK plasmid by enzymatic digestion with Xho I and Sal I. The enhanced green fluorescence protein (EGFP) carrier was extracted from pEGFP by the same procedure. The KDR-TK was inserted into the pEGFP carrier to construct pEGFP-KDR-TK. Using ultrasound irradiation and microbubble, pEGFP-KDR-TK was transferred into human umbilical vein endothelial cells (HUVECs). The transient infection rate was estimated by green fluorescent protein (GFP) expression. Transfected HUVECs, non-transfected HUVECs, and HepG2 cells were cultured in the presence of different concentrations of ganciclovir (GCV), and the killing efficacy of HSV-TK/GCV was analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The recombinant pEGFP-KDR-TK was successfully constructed by inserting the KDR-TK fragment into the pEGFP carrier. Transfected HUVECs showed cytoplasmic green fluorescence, and the transient transfection rate was about 20.3%. Pools of G418-resistant cells exhibited a higher sensitivity to theprodrug/GCV compared to non-transfected HUVECs or non-transfected HepG2 cells, respectively. CONCLUSION: KDR promoter and the suicide gene/prodrug system mediated by diagnostic ultrasound combined with microbubble can significantly kill HUVECs. Such therapy may present a novel and attractive approach to target gene therapy on tumor vessels.展开更多
BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel ...BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel and beneficial drug for DN,no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.AIM To assess the effectiveness and safety of ER antagonists among patients with DN.METHODS The EMBASE,PubMed,MEDLINE,Cochrane,and ClinicalTrials.gov databases were searched without any language restrictions.Relative risks with 95%confidence intervals(CIs)for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software.Publication bias was assessed using Egger’s test with Stata/SE software.RESULTS We enrolled seven studies with six data sets and 5271 participants.The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40%reduction in urinary albumin-to-creatinine ratio than the control group(P<0.0001 and P=0.02,respectively).Subgroup analysis for reductions in estimated glomerular filtration rate(eGFR)showed that for the middle-dosage subgroup,the ER antagonists group exhibited lower eGFR reduction than the control group(P<0.00001;mean difference,0.7095%CI:0.66,0.74).Moreover,significant reductions in systolic and diastolic blood pressure were observed in the invention group.CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor/angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR.However,attention should be given to adverse events,including cardiac failure,anemia,and hypoglycemia,as well as serious adverse events.展开更多
Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is...Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system （SNS） activity and expression of N-methyI-D-aspartic acid （NMDA） receptors in the paraventricular nucleus of the hypothalamus （PVN）. Male rats were classified as ＂sluggish,＂ ＂normal,＂ and ＂rapid＂ ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460±480 mV, 1660±600 mV, and 1680±490 mV, respectively （P = 0.71）. However, SNS sensitivity was remarkably different between the groups （P 〈 0.01）, being 28.9% ± 8.1% in ＂sluggish,＂ 48.4%±7.5% in ＂normal,＂ and 88.7% ~ 7.4% in ＂rapid＂ groups. Compared with ＂normal＂ ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of ＂rapid＂ ejaculators was significantly higher, whereas it was significantly lower in ＂sluggish＂ ejaculators （P = 0.01）. In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity （r = 0.876, P = 0.02）. This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.展开更多
Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potentia...Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.展开更多
Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have re...Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.展开更多
基金Supported by National Natural Science Foundation of China(31201218)National Science and Technology Project of "Twelfth Five Year" Plan of China(2011BAD35B01)+3 种基金Taishan Scholars Program of Shandong Province(Crop Cultivation and Breeding)Basic Research Program of Science and Technology Project of Qingdao City[12-1-4-5-(11)-jch]Starting Fund for High-level Personnel of Qingdao Agricultural University(No.630740)Shandong Key Laboratory of Maize Breeding and Cultivation Techniques
文摘Acetosyringone （AS） has great influences on Agrobacterium-mediated genetic transformation. In order to improve the transformation frequency of waxy maize, in this study, shoot tips and immature embryo-derived callus of Lainongnuo 38 were collected as receptor materials, to compare the effects of pH in suspension medium, addition modes and concentrations of acetosyringone on genetic transformation of waxy maize. Results showed that adding 2 μl of 150 μmol/L AS in the wound with suspension medimn at pH 5.2 can significantly improve the transformation frequency of shoot tips of waxy maize; in genetic transformation of maize callus, adding 5 mg/L AS in infection solution can significantly improve the percentage of resistant callus.
基金supported by the National Natural Science Foundation of China,No.31440047the Natural Science Foundation of Guangdong Province in China,No.2015A030310152
文摘Various studies have reported that galanin can promote axonal regeneration of dorsal root ganglion neurons in vitro and inhibit neuropathic pain. However, little is known about its effects on diabetic peripheral neuropathy, and in vivo experimental data are lacking. We hypothesized that repeated applications of exogenous galanin over an extended time frame may also repair nerve damage in diabetic peripheral neuropathy, and relieve pain in vivo. We found that neuropathic pain occurred in streptozotocin-induced diabetic rats and was more severe after sciatic nerve pinch injury at 14 and 28 days than in diabetic sham-operated rats. Treatment with exogenous galanin alleviated the neuropathic pain and promoted sciatic nerve regeneration more effectively in diabetic rats than in non-diabetic rats after sciatic nerve pinch injury. This was accompanied by changes in the levels of endogenous galanin, and its receptors galanin receptor 1 and galanin receptor 2 in the dorsal root ganglia and the spinal dorsal horn when compared with nerve pinch normal rats. Our results show that application of exogenous galanin daily for 28 days can promote the regeneration of injured sciatic nerves, and alleviate neuropathic pain in diabetic rats.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease in the world.NAFLD is known to be associated with obesity,type 2 diabetes,metabolic syndrome and increased cardiovascular events:for these reasons,it is becoming a global public health problem and represents an important challenge in terms of prevention and treatment.The mechanisms behind the pathogenesis of NAFLD are multiple and have not yet been completely unraveled;consequently,at moment there are not effective treatments.In the past few years a large body of evidence has been assembled that attributes an important role in hepatic aberrant fat accumulation,inflammation and fibrosis,to the vitamin D/vitamin D receptor(VD/VDR)axis,showing a strong association between hypovitaminosis D and the diagnosis of NAFLD.However,the data currently available,including clinical trials with VD supplementation,still provides a contrasting picture.The purpose of this editorial is to provide an overview of recent advances in the pathogenesis of NAFLD in relation to VD/VDR.Based on recent data from literature,we focused in particular on the hypothesis that VDR itself,independently from its traditional ligand VD,may have a crucial function in promoting hepatic fat accumulation.This might also offer new possibilities for future innovative therapeutic approaches in the management of NAFLD.
文摘The European beaver (Castor fiber L.) is the largest free-living rode nt in Eurasia. The prese nt work aimed to determi ne sex- and seas on-related cha nges in leptin receptor (Ob-R) expression in the hypothalamic-pituitary-gonadal/adrenal axes and uterus of beavers during breeding-(April), postbreeding-(July), and pre-breeding-(November) periods. The expression of Ob-R gene and protein was found in all analyzed tissues. The expression of Ob-R mRNA remained constant in the hypothalamus of both sexes during the analyzed stages. Sex- and season-related changes were found in the pituitary gland;the greatest level was observed in July in both sexes. The same expression pattern was noted in the testis, whereas in the ovary a lack of seasonal changes was found. In uterine tissues, the greatest expression occurred in November. The impact of season was also demonstrated in the adrenal cortex. In females, a higher Ob-R transcript level was noted in April, while in males, an increased mRNA abundanee was noted in November than July. Our study suggests that in the beaver, leptin acting via the Ob-R can be an important endocrine factor engaged in the regulation of reproductive functions and stress response.
文摘Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional memories.These receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental monitoring.The ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous system.Insights gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent deficits.Understanding the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's disease.Olfa ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian body.This ectopic expression provides insights into the chemical structures that can activate olfactory receptors.In addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing microbiota.The analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation mechanisms.This review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative processes.Evidence suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous system injuries.
文摘BACKGROUND Beinaglutide,a short-acting glucagon-like polypeptide-1 receptor agonist,has shown variable efficacy in weight reduction and metabolic control in randomized controlled trials(RCTs).AIM To summarize the therapeutic effects of beinaglutide in patients with overweight/obesity with/without type 2 diabetes.METHODS RCTs involving patients receiving beinaglutide in the intervention arm and placebo or active comparator in the control arm were searched through multiple electronic databases.The change from baseline in body weight was the primary outcome;secondary outcomes included changes in body mass index(BMI),waist circumference(WC),blood pressure,glycemic parameters,lipids,and adverse events(AEs).RevMan web was used to conduct meta-analysis using random-effects models.Outcomes were presented as mean differences(MDs),odds ratios(ORs),or risk ratios(RRs)with 95%confidence intervals(95%CIs).RESULTS Six RCTs(n=800)with mostly some concerns about the risk of bias were included.Over 12-24 weeks,beinaglutide 0.1-0.2 mg thrice daily was superior to the control group in reducing total(MD=-3.25 kg,95%CI:-4.52 to-1.98,I^(2)=84%,P<0.00001)and percent(MD=-4.13%,95%CI:-4.87 to-3.39,I^(2)=54%,P<0.00001)body weight reduction.Beinaglutide also outperformed the control group in achieving weight loss by 5%(OR 4.61)and 10%(OR=5.34).The superiority of beinaglutide vs the control group was also found in reducing BMI(MD=-1.22 kg/m^(2),95%CI:-1.67 to-0.77)and WC(MD=-2.47 cm,95%CI:-3.74 to-1.19]).Beinaglutide and the control group had comparable impacts on blood pressure,glycemic parameters,insulin resistance,hepatic transaminases,and lipid profile.Beinaglutide posed higher risks of treatment discontinuation due to AEs(RR=3.15),nausea(RR=4.51),vomiting(RR=8.19),palpitation(RR=3.95),headache(RR=2.87),and dizziness(RR=6.07)than the control.However,the two groups had identical risks of total and serious AEs,diarrhea,fatigue,and hypoglycemia.CONCLUSION Short-term data from RCTs suggested that beinaglutide causes modest benefits in reducing body weight,BMI,and WC,with no significant difference in glycemic and other metabolic endpoints compared to the control arm.Safety data were consistent with those of the other drugs in the glucagon-like polypeptide-1 receptor agonist class.Larger RCTs are warranted to prove the longer-term metabolic benefits of beinaglutide.
基金thankful to Dr.Marina George Kudiyirickal MSc,MJDF-RCS,PhD for providing us the audio core tip of this article.
文摘BACKGROUND Data on the use of glucagon-like peptide-1 receptor agonists(GLP-1RAs)in individuals with type 2 diabetes mellitus(T2DM)during Ramadan fasting is limited.No meta-analysis has summarized the safety and effectiveness of GLP-1RAs in these situations.AIM To evaluate the safety and efficacy of GLP-1RA in patients with T2DM fasting during Ramadan.METHODS Electronic databases were systematically searched for relevant studies that featured GLP-1RA in the intervention arm and other glucose-lowering medications in the control arm.The primary outcome was adverse events(AEs)during Ramadan for both groups;other outcomes included changes in glycemic and anthropometric measures during the peri-Ramadan period.RESULTS Four studies[three randomized-controlled trials with low risk of bias(RoB)and one prospective observational study with serious RoB]involving 754 subjects were analyzed.GLP-1RA group achieved greater glycated hemoglobin reduction than the non-GLP-1RA group[mean difference(MD):-0.31%,95%CI:-0.61 to-0.01,P=0.04,I2=77%]with a lower risk of documented symptomatic hypoglycemia(risk ratio=0.38,95%CI:0.16 to 0.88,P=0.02).Any AEs,serious AEs,or AEs that led to treatment discontinuation were comparable between the two groups.The GLP-1RA group experienced greater weight loss compared to the non-GLP-1RA group(MD:-2.0 kg,95%CI:-3.37 to-0.63,P=0.004,I2=95%).There were comparable changes in blood pressure and lipid profile between the two groups.GLP-1RA users experienced higher risks of gastrointestinal AEs,nausea,and vomiting;however,the risks of heartburn,abdominal pain,and diarrhea were similar in both groups.CONCLUSION Limited evidence suggests that GLP-1RAs are safe for T2DM management during Ramadan,offering modest benefits in blood sugar control and weight loss.Large multicenter trials are needed to confirm their safety and efficacy in at-risk populations,improving clinical practice decision-making.
基金supported by the National Natural Science Foundation of China(81971058,82371226,82101295,82301398)the National Funded Postdoctoral Researcher Program(GZC20233585)The Boost Plan of Xijing Hospital(XJZT24QN25,XJZT25CX22).
文摘Neuropathic pain,often featuring allodynia,imposes significant physical and psychological burdens on patients,with limited treatments due to unclear central mechanisms.Addressing this challenge remains a crucial unsolved issue in pain medicine.Our previous study,using protein kinase C gamma(PKCγ)-tdTomato mice,highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia.However,the regulatory mechanisms governing this circuit necessitate further elucidation.We used diverse transgenic mice and advanced techniques to uncover the regulatory role of the descending serotonin(5-HT)facilitation system on spinal PKCγ neurons.Our findings revealed that 5-HT neurons from the rostral ventromedial medulla hyperpolarize spinal inhibitory interneurons via 5-HT_(2C) receptors,disinhibiting the feedforward inhibitory circuit involving PKCγ neurons and exacerbating allodynia.Inhibiting spinal 5-HT_(2C) receptors restored the feedforward inhibitory circuit,effectively preventing neuropathic allodynia.These insights offer promising therapeutic targets for neuropathic allodynia management,emphasizing the potential of spinal 5-HT_(2C) receptors as a novel avenue for intervention.
基金supported by grants from the Jack Brown and Family Alzheimer’s Disease Research Foundationthe Natural Sciences and Engineering Research Council of Canada(No.2020-04407)+1 种基金the University of British Columbia Okanagan CampusThe authors also thank Gentmed SIA for financial assistance。
文摘Neuroinflammation contributes to a wide range of neurodegenerative diseases including Alzheimer's disease,Parkinson's disease,Huntington's disease,and multiple sclerosis.It is driven by non-neuronal glial cells,mainly microglia and astrocytes.Microglia are the resident immune cells of the central nervous system,while astrocytes are the main support cells for neuronal functions but can also participate in neuroimmune responses.Both these glial cell types can become reactive upon detection of certain endogenous intracellular molecules that appear in the extracellular space under specific circumstances;these can be pathology-associated abnormal structures,such as amyloidβproteins,or damage-associated molecular patterns released from injured cells,including their mitochondria.Once in the extracellular space,damage-associated molecular patterns act as ligands for specific pattern recognition receptors expressed by glia inducing their reactivity and neuroimmune responses.This review considers the following mitochondrial damage-associated molecular patterns:heme,cytochrome c,cardiolipin,adenosine triphosphate,mitochondrial DNA,mitochondrial transcription factor A,N-formyl peptides,and the tricarboxylic acid cycle metabolites:succinate,fumarate,and itaconate.We describe their well-established functions as damage-associated molecular patterns of the peripheral tissues before summarizing available evidence indicating these molecules may also play significant roles in the neuroimmune processes of the central nervous system.We highlight the pattern recognition receptors that mitochondrial damage-associated molecular patterns interact with and the cellular signaling mechanisms they modulate.Our review demonstrates that some mitochondrial damage-associated molecular patterns,such as cytochrome c,adenosine triphosphate,and mitochondrial transcription factor A,have already demonstrated significant effects on the central nervous system.In contrast,others including cardiolipin,mitochondrial DNA,N-formyl peptides,succinate,fumarate,and itaconate,will require additional studies corroborating their roles as damageassociated molecular patterns in the central nervous system.For all of the reviewed mitochondrial damage-associated molecular patterns,there is a shortage of studies using human cells and tissues,which is identified as a significant knowledge gap.We also assess the need for targeted research on the effects of mitochondrial damage-associated molecular patterns in the central nervous system pathologies where their roles are understudied.Such studies could identify novel treatment strategies for multiple neurodegenerative diseases,which are characterized by chronic neuroinflammation and currently lack effective therapies.
基金supported by grants from Tianjin Scientific Research Project in Key Areas of Traditional Chinese Medicine,Tianjin Municipal Health Commission,No.2024012(to JL)Tianjin Municipal Education Commission Project,No.2021KJ217(to CS)。
文摘Peroxisome proliferator-activated receptor alpha is a member of the nuclear hormone receptor superfamily and functions as a transcription factor involved in regulating cellular metabolism.Previous studies have shown that PPARαplays a key role in the onset and progression of neurodegenerative diseases.Consequently,peroxisome proliferator-activated receptor alpha agonists have garnered increasing attention as potential treatments for neurological disorders.This review aims to clarify the research progress regarding peroxisome proliferator-activated receptor alpha in nervous system diseases.Peroxisome proliferator-activated receptor alpha is present in all cell types within adult mouse and adult neural tissues.Although it is conventionally believed to be primarily localized in the nucleus,its function may be regulated by a dynamic balance between cytoplasmic and nuclear shuttling.Both endogenous and exogenous peroxisome proliferator-activated receptor alpha agonists bind to the peroxisome proliferator-activated response element to exert their biological effects.Peroxisome proliferator-activated receptor alpha plays a significant therapeutic role in neurodegenerative diseases.For instance,peroxisome proliferator-activated receptor alpha agonist gemfibrozil has been shown to reduce levels of soluble and insoluble amyloid-beta in the hippocampus of Alzheimer's disease mouse models through the autophagy-lysosomal pathway.Additionally,peroxisome proliferator-activated receptor alpha is essential for the normal development and functional maintenance of the substantia nigra,and it can mitigate motor dysfunction in Parkinson's disease mouse models.Furthermore,peroxisome proliferator-activated receptor alpha has been found to reduce neuroinflammation and oxidative stress in various neurological diseases.In summary,peroxisome proliferator-activated receptor alpha plays a crucial role in the onset and progression of multiple nervous system diseases,and peroxisome proliferator-activated receptor alpha agonists hold promise as new therapeutic agents for the treatment of neurodegenerative diseases,providing new options for patient care.
文摘Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.
基金supported by the National Natural Science Foundation of China(Nos.82174091,82122066,81973291,and 82003909)the National Key R&D Program of China(No.2022YFC2704603).
文摘Insomnia is a common sleep disorder without effective therapy and can affect a person's life.The mechanism of the disease is not completely understood.Hence,there is a need to understand the targets related to insomnia,in order to develop innovative therapies and new compounds.Recently,increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia.Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain.In this review,the role of 5-hydroxytryptamine(5-HT)in insomnia development is summarized,while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes,in order to provide reference for subsequent research.
基金Supported by Grants from National Institutes of Health,1R01 HL085499 to Yang Q, NO.1R01 HL084456,and NO.T32 HL007457 to Kim Tthe ADA Basic Science Award,#7-12-BS-208,to Yang Q
文摘Peroxisome-proliferator-activated receptors(PPARs) comprise three subtypes(PPARα,δ and γ) to form a nuclear receptor superfamily.PPARs act as key transcriptional regulators of lipid metabolism,mitochondrial biogenesis,and anti-oxidant defense.While their roles in regulating lipid metabolism have been well established,the role of PPARs in regulating redox activity remains incompletely understood.Since redox activity is an integral part of oxidative metabolism,it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state.The effects of PPAR signaling are directly related to PPAR expression,protein activities and PPAR interactions with their coregulators.The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue.Adding to the complexity,specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways.Moreover,the intensity and extension of redoxregulation by each PPAR subtype are varied depending on different tissues and cell types.Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups.The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms,as well as to discuss the implications in the cardiovascular system.
基金Supported by Zhejiang provincial top key discipline in surgery
文摘AIM:To investigate the relationship between polymorphisms present in the vitamin D receptor(VDR) gene and colorectal cancer risk,a systematic meta-analysis of population-based studies was performed.METHODS:A total of 38 relevant reports published between January 1990 and August 2010 were identified,of which only 23 qualified for this meta-analysis based on our selection criteria.Five polymorphic variants of the VDR gene,including Cdx-2(intron 1e) and FokI(exon 2) present in the 5' region of the gene,and BsmI(intron 8),ApaI(intron 8),and TaqI(exon 9) sites present in the 3' untranslated region(UTR),were evaluated for possible associations with colorectalcancer risk.Review manager 4.2 was used to perform statistical analyses.RESULTS:In the meta-analysis performed,only the BsmI polymorphism was found to be associated with colorectal cancer risk.In particular,the BsmI B genotype was found to be related to an overall decrease in the risk for colorectal cancer [BB vs bb:odds ratio(OR) = 0.87,95% CI:0.80-0.94,P = 3 × 10-4;BB vs Bb + bb:OR = 0.90,95% CI:0.84-0.97,P = 5 × 10-4].Moreover,in subgroup analyses,the BsmI B genotype was significantly associated with colon cancer,and not rectal cancer.An absence of between-study heterogeneity was also observed.CONCLUSION:A meta-analysis of 23 published studies identified the BsmI polymorphism of the VDR gene to be associated with an increased risk of colon cancer.
文摘The biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors,which include epidermal growth factor receptor agonists and members of the transforming growth factor β family.Furthermore,the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small,immunomodulatory proteins also play key roles in carcinogenesis and may,therefore,be potential targets for novel therapeutic approaches.In this review,we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.
基金New Century Distinguished Scholar Supporting Program of Ministry of Education (80000-3171404) The National Natural Science Foundation of China, No. 30300082, No. 30470467
文摘AIM: To investigate the killing efficiency of a recombinant plasmid containing a thymidine kinase (TK) domain insert driven by the vascular endothelial growth factor receptor 2 (VEGFR2) promoter (KDR) on vascular endothelial cells.METHODS: The KDR-TK fragment was extracted from pBluescript Ⅱ KDR-TK plasmid by enzymatic digestion with Xho I and Sal I. The enhanced green fluorescence protein (EGFP) carrier was extracted from pEGFP by the same procedure. The KDR-TK was inserted into the pEGFP carrier to construct pEGFP-KDR-TK. Using ultrasound irradiation and microbubble, pEGFP-KDR-TK was transferred into human umbilical vein endothelial cells (HUVECs). The transient infection rate was estimated by green fluorescent protein (GFP) expression. Transfected HUVECs, non-transfected HUVECs, and HepG2 cells were cultured in the presence of different concentrations of ganciclovir (GCV), and the killing efficacy of HSV-TK/GCV was analyzed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide (MTT) assay. RESULTS: The recombinant pEGFP-KDR-TK was successfully constructed by inserting the KDR-TK fragment into the pEGFP carrier. Transfected HUVECs showed cytoplasmic green fluorescence, and the transient transfection rate was about 20.3%. Pools of G418-resistant cells exhibited a higher sensitivity to theprodrug/GCV compared to non-transfected HUVECs or non-transfected HepG2 cells, respectively. CONCLUSION: KDR promoter and the suicide gene/prodrug system mediated by diagnostic ultrasound combined with microbubble can significantly kill HUVECs. Such therapy may present a novel and attractive approach to target gene therapy on tumor vessels.
文摘BACKGROUND Diabetic nephropathy(DN)is the main cause of chronic kidney disease and endstage renal disease worldwide.Although available clinical trials have shown that endothelin receptor(ER)antagonists may be a novel and beneficial drug for DN,no consistent conclusions regarding their sufficient effectiveness and safety for patients with DN have been presented.AIM To assess the effectiveness and safety of ER antagonists among patients with DN.METHODS The EMBASE,PubMed,MEDLINE,Cochrane,and ClinicalTrials.gov databases were searched without any language restrictions.Relative risks with 95%confidence intervals(CIs)for dichotomous data and mean differences or standardized mean difference with 95%CIs for continuous data were calculated using Review Manager 5.3 software.Publication bias was assessed using Egger’s test with Stata/SE software.RESULTS We enrolled seven studies with six data sets and 5271 participants.The ER antagonists group showed a significantly greater reduction in albuminuria and more patients with 40%reduction in urinary albumin-to-creatinine ratio than the control group(P<0.0001 and P=0.02,respectively).Subgroup analysis for reductions in estimated glomerular filtration rate(eGFR)showed that for the middle-dosage subgroup,the ER antagonists group exhibited lower eGFR reduction than the control group(P<0.00001;mean difference,0.7095%CI:0.66,0.74).Moreover,significant reductions in systolic and diastolic blood pressure were observed in the invention group.CONCLUSION ER blockades combined with angiotensin converting enzyme inhibitor/angiotensin II type 1 receptor blockers may be an effective treatment to lower blood pressure and reduce proteinuria in DN with declined eGFR.However,attention should be given to adverse events,including cardiac failure,anemia,and hypoglycemia,as well as serious adverse events.
文摘Differences in intravaginal ejaculation latency reflect normal biological variation, but the causes are poorly understood. Here, we investigated whether variation in ejaculation latency in an experimental rat model is related to altered sympathetic nervous system （SNS） activity and expression of N-methyI-D-aspartic acid （NMDA） receptors in the paraventricular nucleus of the hypothalamus （PVN）. Male rats were classified as ＂sluggish,＂ ＂normal,＂ and ＂rapid＂ ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. The lumbar splanchnic nerve activity baselines in these groups were not significantly different at 1460±480 mV, 1660±600 mV, and 1680±490 mV, respectively （P = 0.71）. However, SNS sensitivity was remarkably different between the groups （P 〈 0.01）, being 28.9% ± 8.1% in ＂sluggish,＂ 48.4%±7.5% in ＂normal,＂ and 88.7% ~ 7.4% in ＂rapid＂ groups. Compared with ＂normal＂ ejaculators, the percentage of neurons expressing NMDA receptors in the PVN of ＂rapid＂ ejaculators was significantly higher, whereas it was significantly lower in ＂sluggish＂ ejaculators （P = 0.01）. In addition, there was a positive correlation between the expression of NMDA receptors in the PVN and SNS sensitivity （r = 0.876, P = 0.02）. This study shows that intravaginal ejaculatory latency is associated with SNS activity and is mediated by NMDA receptors in the PVN.
基金supported by grants from the Project of Scientific and Technologic Bureau of Guangzhou City(Grant No.202201010165)the Key Project of Scientific and Technologic Bureau of Guangzhou City(Grant No.202201020335).
文摘Gender disparities are evident across different types of digestive system cancers,which are typically characterized by a lower incidence and mortality rate in females compared to males.This finding suggests a potential protective role of female steroid hormones,particularly estrogen,in the development of these cancers.Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors(ERs),including the classic(ERαand ERβ)and non-traditional ERs[G protein-coupled estrogen receptor(GPER)].Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers.In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers,including hepatocellular,pancreatic,esophageal,gastric,and colorectal carcinoma.Furthermore,we discuss the potential molecular mechanisms underlying ERα,ERβ,and GPER effects,and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs.The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved.Additionally,deciphering the intricate roles of estrogen,ERs,and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers,eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.
文摘Attention deficit hyperactivity disorder （ADHD） is one of the most common mental disorders in childhood, with a high heritability about 60% to 90%. Serotonin is a monoamine neurotransmitter. Numerous studies have reported the association between the serotonin receptor family （5-HTR） gene polymorphisms and ADHD, but the results are still controversial. In this study, we conducted a meta-analysis of the association between 5-HTRIB, 5-HTR2A, and 5-HTR2C genetic variants and ADHD. The results showed that the 861G allele of 5-HTRIB SNP rs6296 could significantly increase the risk of ADHD （OR= 1.09, 95% CI： 1.01-1.18）; the 5-HTR2C gene rs518147 （OR=1.69, 95% CI： 1.38-2.07） and rs3813929 （OR = 1.57, 95% CI： 1.25-1.97） were all associated with the risk of ADHD. In addition, we also carried on a case- control study to explore the relevance between potential candidate genes 5-HTR1A, 5-HTRIE, 5-HTR3A and ADHD. The results indicated that 5-HTRIA rs6295 genotype （CC＋CG vs. GG OR=Z00, 95% CI： 1.23-3.27） and allele （OR=1.77, 95% CI： 1.16-2.72） models were statistically significantly different between case group and control group. This study is the first comprehensive exploration and summary of the association between serotonin receptor family genetic variations and ADHD, and it also provides more evidence for the etiology of ADHD.
