Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is be...Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner.展开更多
The use of artificial intelligence(AI)in wound care has become a crucial instrument in improving the diagnosis,treatment,and management of chronic wounds.This study examines the several functions of AI in wound care,e...The use of artificial intelligence(AI)in wound care has become a crucial instrument in improving the diagnosis,treatment,and management of chronic wounds.This study examines the several functions of AI in wound care,emphasizing its ability to better wound evaluation,hasten healing,alleviate pain,and improve cost-effectiveness.AI-driven technology,including mobile applications and intelligent bandages,provides precise wound assessment,tissue analysis,and continuous monitoring,hence allowing for tailored treatment strategies and prompt intervention.Moreover,AI-driven algorithms forecast wound healing trajectories and find individuals susceptible to chronic wounds,allowing prompt preventative interventions.There are also practical issues with integrating it into clinical practice.Adding AI to current healthcare systems,like electronic medical records(EMRs),needs careful planning and teamwork to make sure that AI-driven insights are used well in real-time clinical decision-making.To make sure AI is used safely,legal frameworks need to be set up to provide clear rules for its use in healthcare.These frameworks should include openness,risk management,and data evaluation.Lastly,clinical validation and acceptance are still big problems.Many AI-powered tools don't have enough clinical validation and aren't widely available,which makes it hard to use them in everyday clinical practice.Solving these problems is important for getting the most out of AI in wound care and making sure it is used safely and effectively.The article combines current advancements and prospective trajectories in AI-assisted wound care,highlighting its revolutionary ability to revolutionize patient outcomes and healthcare delivery.展开更多
Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessi...Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.展开更多
Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits...Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits from the use of Azolla spp.for nitrogen supply.By virtue of their symbiosis with the nitrogen-fixing cyanobacterium Trichormus azollae,Azolla spp.are ferns that release nitrogen into the environment upon biomass decomposition.However,whether and to what extent actively growing Azolla plants influence the development of co-cultivated rice seedlings remains unclear.To address this,rice(Oryza sativa L.var.Kitaake)seedlings were co-cultivated hydroponically with Azolla filiculoides for up to two months.Morphological changes in rice roots and aerial organs were assessed alongside nitric oxide assays in rice roots,root transcriptomics,and targeted hormonomics of rice roots,leaves,and growth media.Here,we showed that co-cultivation with actively growing A.filiculoides alters rice root architecture by inducing a nitric oxide boost and accelerates leaf and tiller differentiation and proliferation.Overall,this study provides an in-depth analysis of the morphogenetic effects of co-cultivated A.filiculoides on rice during early vegetative growth.It also paves the way for studies assessing whether A.filiculoides co-cultivation primes rice plants to better withstand abiotic and biotic stresses.展开更多
High-entropy alloy composites(HEACs)have attracted significant attention due to their exceptional mechanical properties and chemical stability.By adjusting the content of reinforcing particles in the high-entropy allo...High-entropy alloy composites(HEACs)have attracted significant attention due to their exceptional mechanical properties and chemical stability.By adjusting the content of reinforcing particles in the high-entropy alloy and by employing advanced additive manufacturing techniques,high-performance HEACs can be fabricated.However,there is still considerable room for improvement in their performance.In this study,CoCrFeMnNi HEA powders were used as the matrix,and NiCoFeAlTi high-entropy intermetallic powders were used as the high-entropy reinforcement(HER).CoCrFeMnNi/NiCoFeAlTi HEACs were fabricated using selective laser melting technology.The study results indicate that after aging,the microstructure of HEACs with HER exhibits Al-and Ti-rich nano-oxide precipitates with an orthorhombic CMCM type structure system.After aging at 873 K for 2 h,HEACs with HER achieved excellent overall mechanical properties,with an ultimate tensile strength of 731 MPa.This is attributed to the combined and synergistic effects of precipitation strengthening,dislocation strengthening,and the high lattice distortion caused by high intragranular defects,which provide a multi-scale strengthening and hardening mechanism for the plastic deformation of HEACs with HER.This study demonstrates that aging plays a crucial role in controlling the precipitate phases in complex multi-element alloys.展开更多
TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity ...TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.展开更多
Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry.The existing management practices are insufficient to ful...Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry.The existing management practices are insufficient to fully prevent heat stress with an urgent need to develop preventive medicines.The aim of this study was to develop an antiheat stress Chinese herbal formula(CHF)via big data analysis techniques and to evaluate its anti-heat stress effect and mechanism of action via pharmacodynamic evaluation and network pharmacology analysis.Many anti-heat stress CHFs were collected from the Chinese National Knowledge Infrastructure(CNKI)database.Three alternative CHFs were obtained via unsupervised entropy hierarchical clustering analysis,and the most effective CHF against heat stress,Shidi Jieshu decoction(SJD),was obtained by screening in a mouse heat stress model.In dry and hot environments,SJD significantly improved the heat tolerance of AA broilers by 4-6℃.In a humid and hot environment,pretreatment with 2%SJD resulted in 100%survival of Wenchang chickens at high temperatures.The main active ingredients of SJD were identified as muntjacoside E,timosaponin C,macrostemonoside H and mangiferin via ultraperformance liquid chromatography/mass spectrometry(UPLC/MS)and database comparison.The active ingredients of SJD were found to target tumor necrosis factor-α(TNF-α),signal transducer activator of transcription 3(STAT3)and epidermal growth factor receptor(EGFR).Finally,the safety of the new formulation was assessed in an acute oral toxicity study in rats.The SJDs developed in this study provide a new option for the prevention of heat stress in animal husbandry and offer new insights for further research on anti-heat stress.展开更多
Despite their biodegradability and economic advantage, plant leaves used as packaging can constitute a public health problem. The aim of this study was to characterize the microbial diversity contaminating plant leave...Despite their biodegradability and economic advantage, plant leaves used as packaging can constitute a public health problem. The aim of this study was to characterize the microbial diversity contaminating plant leaves used as food packaging. In total, two hundred and forty (240) samples composed of Thaumatococcus daniellii and Musa paradisiaca leaves were collected and analyzed. Microbial diversity was assessed using specific medium and biochemical tests. The resistance profile was determined by the Müeller-Hinton agar diffusion method. The resistance (blaSHV, blaIMP, blaTEM) and biofilm formation (pslA, pelA) genes were searched by PCR method. Plant leaves were contaminated by bacterial (68.7%) and fungal (100%) strains. Extreme bacterial (7.1 log10 cfu/cm2) and fungal (3.5 log10 cfu/cm2) loads were obtained on Thaumatococcus daniellii leaves. Bacterial prevalence was 45.1% (S. aureus), 38.8% (E. coli) and 16.1 (P. aeruginosa). In order of decreasing importance, the prevalence of fungal species was 41.1% (A. flavus), 33.1% (A. fumigattus), 13.7% (A. niger) and 12.1% Candida sp. Resistance of E. coli to penicillins ranges from 31.6% to 87.3% and to cephalosporins from 13.3% to 28%. The P. aeruginosa strains were mainly resistant to aztreonam (87.6%). Those of S. aureus showed resistance to tetracycline (67.6), vancomycin (53), erythromycin (44.6) and levofloxacin (32.7). The blaSHV (14.28% to 18.60%) and blaIMP (9.52% to 16.28%) genes were detected in the bacterial strains. P. aeruginosa strains (19.05%) harbored the pslA and pelA genes. The health safety of these biodegradable plant-based packaging contributes to their valorization.展开更多
Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multi...Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multiple side effects.Therefore,there is a pressing need for safe and effective anti-diabetic medications.Traditional Chinese medicine has recognized Lycium barbarum(LB;goji berry)plant,commonly known as“wolfberry fruit”in China,for over 2,000 years.Natural compounds derived from LB show promise in reducing diabetes levels.Although research on the impact of LB on diabetes is still limited,our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved.LB can modulate diabetes through various pathways,such as inhibitingα-amylase andα-glucosidase activities,promotingβ-cell proliferation,stimulating insulin secretion,inhibiting glucagon secretion,improving insulin resistance and glucose tolerance,and enhancing antioxidant and anti-inflammatory activities.Additionally,LB improves gut flora and immunomodulation,further aiding diabetes management.These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.展开更多
Dentisphaera Páll-Gergely&Jochum,2017 is a troglobitic land snails genus known to harbour only one species found in a single cave in North Vietnam.Based on recently collected specimens from China,three specie...Dentisphaera Páll-Gergely&Jochum,2017 is a troglobitic land snails genus known to harbour only one species found in a single cave in North Vietnam.Based on recently collected specimens from China,three species,Dentisphaera lagredeae Chen,Grego&Páll-Gergely,sp.nov.,Dentisphaera shzha Chen,Grego&Páll-Gergely,sp.nov.and Dentisphaera zhoui Chen,Lin&Páll-Gergely,sp.nov.are introduced as new to science.The distribution range of Dentisphaera is extended based on the collecting records of these new species.展开更多
In aquaculture, feed represents the main component of production costs, and the development of this sector depends on the development of an economical feed formulation that meets the qualitative and quantitative requi...In aquaculture, feed represents the main component of production costs, and the development of this sector depends on the development of an economical feed formulation that meets the qualitative and quantitative requirements of fish. The aim of this study was to determine the nutritive and microbiological quality of fish feed formulated from local flours enriched with Hermetia illucens larvae. The raw materials used for formulation were fishmeal, corn meal, low-grade rice, soybean meal and Hermetia illucens larvae meal. Different iso-protein feed compositions were prepared with 0%, 10%, 25%, 35%, 50%, 65%, 75% and 100% incorporation of Hermetia illucens larvae meal as a substitute for fish meal. Biochemical and microbiological analyses of these flours were determined using standard methods. The results showed that incorporation of larvae meal had an influence on the biochemical characteristics ash (8.15 to 20.27%), lipid (11.55 to 24.94%), fiber (13.93 to 20.41%) and dry matter (89.65 to 91.19%) of various formulated feed. Loads of fecal Streptococci, Staphylococci, Aeromonas, yeasts and molds ranged from 2.4 to 4.9 log 10 CFU/g;3.6 to 3.9 log 10 CFU/g;2.2 to 2.7 log 10 CFU/g;2.1 to 2.3 log 10 CFU/g, respectively. The level of contamination of these flours was below the microbiological criteria applicable to animal feed. Feed formulated with 0% and 10% Hermetia illucens larvae showed the best nutritive and microbiological characteristics. These results suggest that flours enriched with Hermetia illucens larvae could be used in fish feed.展开更多
The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications direct...The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications directly addressing the research problem at hand.Similarly,while the body of work on optimal location and sizing of renewable energy generators(REGs)in balanced distribution systems is substantial,only the most pertinent sources are cited,aligning closely with the study’s objective function.A comprehensive literature review reveals several key research areas:RES integration,RES-related optimization techniques,strategic placement of wind and solar generation,and RES promotion in deregulated powermarkets,particularly within transmission systems.Furthermore,the optimal location and sizing of REGs in both balanced and unbalanced distribution systems have been extensively studied.RESs demonstrate significant potential for standalone applications in remote areas lacking conventional transmission and distribution infrastructure.Also presents a thorough review of current modeling and optimization approaches for RES-based distribution system location and sizing.Additionally,it examines the optimal positioning,sizing,and performance of hybrid and standalone renewable energy systems.This paper provides a comprehensive review of current modeling and optimization approaches for the location and sizing of Renewable Energy Sources(RESs)in distribution systems,focusing on both balanced and unbalanced networks.展开更多
The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research ...The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.展开更多
OBJECTIVE:To explore the potential of combining natural herbs like chamomile and saffron for the management of anxiety and depression.METHODS:A rodent model of Major Depressive Disorder(MDD)and anxiety,secondary to st...OBJECTIVE:To explore the potential of combining natural herbs like chamomile and saffron for the management of anxiety and depression.METHODS:A rodent model of Major Depressive Disorder(MDD)and anxiety,secondary to streptozotocin-induced diabetes mellitus was made.A total of 6 rat groups were chosen;healthy and diseased controls;and diseased test groups of fluoxetine,saffron,chamomile,and combined saffron and chamomile treated(n=6/group).Activity by forced swim test(FST),elevated plus maze test(EPMT),and correlations with biochemical markers like serum glucose,tryptophan,C-reactive protein(CRP),brain derived neurotrophic factor(BDNF)and 5-hydroxytryptamine 2C receptor(5HT2CR)expression,were assessed at the end of the 3rd week of the treatment.A one-way analysis of variance with a post-hoc Tukey's test was applied.RESULTS:The combined herbal treatment group showed significantly better(P<0.05)than all other groups in terms of anti-hyperglycemic effect.All treatments improved the CRP levels;however,the combination group was also significantly better than fluoxetine and the individual herb groups.Only the herb groups showed efficacy in the FST with added benefits of the combination group over the healthy controls and similar trends in the EPMT.However,expression of 5HT2CR was repressed while BDNF was elevated through treatment.CONCLUSION:This study shows that in comparison to treatment with a SSRI,and individual herbs,the combination of chamomile and saffron showed overall improved outcomes.展开更多
Nuclear receptors(NRs)function as crucial transcription factors in orchestrating essential functions within the realms of development,host defense,and homeostasis of body.NRs have garnered increased attention due to t...Nuclear receptors(NRs)function as crucial transcription factors in orchestrating essential functions within the realms of development,host defense,and homeostasis of body.NRs have garnered increased attention due to their potential as therapeutic targets,with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression.Consequently,these pharmacological agents hold promise for the treatment and management of various diseases.Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs(miRNAs)in chronic inflammation,disease progression,and therapy resistance,primarily by modulating transcription factors,particularly NRs.By exploiting inflammatory pathways such as protein kinase B(Akt)/mammalian target of rapamycin(mTOR),nuclear factor kappa-B(NF-κB),signal transducer and activator of transcription 3(STAT3),and Wnt/β-catenin signaling,exosomes and NRs play a pivotal role in the panorama of development,physiology,and pathology.The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades,influencing various processes in recipient cells such as survival,proliferation,differentiation,metabolism,and cellular defense mechanisms.This comprehensive review meticulously examines the involvement of exosome-mediated NRs regulation in the pathogenesis of chronic ailments,including atherosclerosis,cancer,diabetes,liver diseases,and respiratory conditions.Additionally,it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs,leading to immunomodulation.Furthermore,it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation,delineates current limitations,and provides insights into future perspectives.This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.展开更多
MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and patholog...MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.展开更多
AIM： To evaluate the ability of Curcuma Ionga （CL） and Tinospora cordifolia （TC） formulation to prevent anti-tuberculosis （TB） treatment （ATT） induced hepatotoxicity. METHODS： Patients with active TB diagnos...AIM： To evaluate the ability of Curcuma Ionga （CL） and Tinospora cordifolia （TC） formulation to prevent anti-tuberculosis （TB） treatment （ATT） induced hepatotoxicity. METHODS： Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched （25%） CL and a hydro-ethanolic extract enriched （50%） TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS： Incidence and severity of hepatotoxicity was significantly lower in trial group （incidence： 27/192 vs 2/316, P 〈 0.0001）. Mean aspartate transaminase （AST） （195.93 ± 108.74 vs 85 ± 4.24, P 〈 0.0001）, alanine transaminase （ALT） （75.74 ± 26.54 vs 41 ± 1.41, P 〈 0.0001） and serum bilirubin （5.4 ±3.38 vs 1.5 ±0.42, P 〈 0.0001）. A lesser sputum positivity ratio at the end of 4 wk （10/67 vs 4/137, P = 0.0068） and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment （9/152 vs 2/278, P = 0.0037） was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group （P 〈 0.0001）. CONCLUSION： The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.展开更多
AIM:To investigate the correlations between selfreported symptoms of irritable bowel syndrome(IBS) and the gastrointestinal(GI) microbiota composition.METHODS:Fecal samples were collected from a total of 44 subjects d...AIM:To investigate the correlations between selfreported symptoms of irritable bowel syndrome(IBS) and the gastrointestinal(GI) microbiota composition.METHODS:Fecal samples were collected from a total of 44 subjects diagnosed with IBS.Their symptoms were monitored with a validated inflammatory bowel disease questionnaire adjusted for IBS patients.Thirteen quantitative real-time polymerase chain reaction assays were applied to evaluate the GI microbiota composition.Eubacteria and GI bacterial genera(Bifidobacterium,Lactobacillus and Veillonella),groups(Clostridium coccoides/Eubacterium rectale,Desulfovibrio desulfuricans) and distinct bacterial phylotypes [closest 16S rDNA sequence resemblance to species Bifidobacterium catenulatum,Clostridium cocleatum,Collinsella aerofaciens(C.aerofaciens),Coprococcus eutactus(C.eutactus),Ruminococcus torques and Streptococcus bovis ] with a suspected association with IBS were quantified.Correlations between quantities or presence/absence data of selected bacterial groups or phylotypes and various IBSrelated symptoms were investigated.RESULTS:Associations were observed between subjects' self-reported symptoms and the presence or quantities of certain GI bacteria.A Ruminococcus torques(R.torques)-like(94% similarity in 16S rRNA gene sequence) phylotype was associated with severity of bowel symptoms.Furthermore,among IBS subjects with R.torques 94% detected,the amounts of C.cocleatum 88%,C.aerofaciens-like and C.eutactus 97% phylotypes were significantly reduced.Interesting observations were also made concerning the effect of a subject's weight on GI microbiota with regard to C.aerofaciens like phylotype,Bifidobacterium spp.and Lactobacillus spp.CONCLUSION:Bacteria seemingly affecting the symptom scores are unlikely to be the underlying cause or cure of IBS,but they may serve as biomarkers of the condition.展开更多
Plants have been used as good bio-indicators and genetic toxicity of environmental pollution in recent years. In this study, aquatic plants Hydrilla verticillata and Ceratophyllum demersum treated with 10umol/L Cd, 5 ...Plants have been used as good bio-indicators and genetic toxicity of environmental pollution in recent years. In this study, aquatic plants Hydrilla verticillata and Ceratophyllum demersum treated with 10umol/L Cd, 5 umol/L Hg, and 20 umol/L Cu for 96 h, showed changes in chlorophyll, protein content, and in DNA profiles. The changes in DNA profiles included variation in band intensity, presence or absence of certain bands and even appearance of new bands. Genomic template stability test performed for the qualitative measurement of changes in randomly amplified polymorphic DNA （RAPD） profiles, showed significant effect at the given concentration of metals. Cloning and sequencing of bands suggested that these markers although may not be homologous to any known gene but its conversion as a sequence characterized amplified region （SCAR） marker is useful in detecting the effects of genotoxin agents.展开更多
基金supported by a BBSRC CASE training studentship,No.BB/K011413/1(to KG)。
文摘Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's disease.The accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased connectivity.However,the precise cellular and molecular mechanisms governing this response remain unknown.In this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture geometry.We utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized medicine.Additionally,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite inhibition.We demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite growth.Thereby,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patient-specific manner.
文摘The use of artificial intelligence(AI)in wound care has become a crucial instrument in improving the diagnosis,treatment,and management of chronic wounds.This study examines the several functions of AI in wound care,emphasizing its ability to better wound evaluation,hasten healing,alleviate pain,and improve cost-effectiveness.AI-driven technology,including mobile applications and intelligent bandages,provides precise wound assessment,tissue analysis,and continuous monitoring,hence allowing for tailored treatment strategies and prompt intervention.Moreover,AI-driven algorithms forecast wound healing trajectories and find individuals susceptible to chronic wounds,allowing prompt preventative interventions.There are also practical issues with integrating it into clinical practice.Adding AI to current healthcare systems,like electronic medical records(EMRs),needs careful planning and teamwork to make sure that AI-driven insights are used well in real-time clinical decision-making.To make sure AI is used safely,legal frameworks need to be set up to provide clear rules for its use in healthcare.These frameworks should include openness,risk management,and data evaluation.Lastly,clinical validation and acceptance are still big problems.Many AI-powered tools don't have enough clinical validation and aren't widely available,which makes it hard to use them in everyday clinical practice.Solving these problems is important for getting the most out of AI in wound care and making sure it is used safely and effectively.The article combines current advancements and prospective trajectories in AI-assisted wound care,highlighting its revolutionary ability to revolutionize patient outcomes and healthcare delivery.
基金Department of Biotechnology(DBT,Govt of India)(BT/PR31315/MED/32/667/2019)DBT along with Wadhwani Research Center for Bioengineering,IIT Bombay(BT/INF/22/SP23026/2017)Department of Biotechnology(DBT,Govt of India)(BT/INF/22/SP17358/2016).
文摘Background:Targeted T-cell therapy has emerged as a promising strategy for the treatment of hematological malignancies.However,its application to solid tumors presents significant challenges due to the limited accessibility and heterogeneity.Localized delivery of tumor-specific T-cells using biomaterials has shown promise,however,procedures required for genetic modification and generation of a sufficient number of tumor-specific T-cells ex vivo remain major obstacles due to cost and time constraints.Methods:Polyethylene glycol(PEG)-based three-dimensional(3D)scaffolds were developed and conjugated with positively charged poly-L-lysine(PLL)using carbamide chemistry for efficient loading of lentiviruses(LVs)carrying tumor antigen-specific T-cell receptors(TCRs).The physical and biological properties of the scaffold were extensively characterized.Further,the scaffold loaded with OVA-TCR LVs was implanted in B16F10 cells expressing ovalbumin(B16-OVA)tumor model to evaluate the anti-tumor response and the presence of transduced T-cells.Results:Our findings demonstrate that the scaffolds do not induce any systemic inflammation upon subcutaneous implantation and effectively recruit T-cells to the site.In B16-OVA melanoma tumor-bearing mice,the scaffolds efficiently transduce host T-cells with OVA-specific TCRs.These genetically modified T-cells exhibit homing capability towards the tumor and secondary lymphoid organs,resulting in a significant reduction of tumor size and systemic increase in anti-tumor cytokines.Immune cell profiling revealed a significantly high percentage of transduced T-cells and a notable reduction in suppressor immune cells within the tumors of mice implanted with these scaffolds.Conclusions:Our scaffold-based T-cell therapy presents an innovative in situ localized approach for programming T-cells to target solid tumors.This approach offers a viable alternative to in vitro manipulation of T-cells,circumventing the need for large-scale in vitro generation and culture of tumor-specific T-cells.It offers an off-the-shelf alternative that facilitates the use of host cells instead of allogeneic cells,thereby,overcoming a major hurdle.
基金carried out within the PRIN project 2017 (Prot.2017N5LBZK): A multidisciplinary approach to gain sustainable improvement of rice productivity through the co-cultivation with the fern Azolla and its cyanobacterial symbiont financed by the Italian Ministry of Research (MUR), the Agritech National Research Center that received funding from the European Union Next-Generation EU (PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR) – MISSIONE 4 COMPONENTE 2, INVESTIMENTO 1.4 – D.D. 1032 17/06/2022, CN00000022)within the Tow Ards Next GENeration Crops Project, reg. no. CZ.02.01.01/00/22_008/0004581 of the ERDF program Johannes Amos Comeniusfunded by ‘ON Foods’ - Research and innovation network on food and nutrition Sustainability, Safety and Security – Working ON Foods B83C22004790001 PE_00000003 project.
文摘Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits from the use of Azolla spp.for nitrogen supply.By virtue of their symbiosis with the nitrogen-fixing cyanobacterium Trichormus azollae,Azolla spp.are ferns that release nitrogen into the environment upon biomass decomposition.However,whether and to what extent actively growing Azolla plants influence the development of co-cultivated rice seedlings remains unclear.To address this,rice(Oryza sativa L.var.Kitaake)seedlings were co-cultivated hydroponically with Azolla filiculoides for up to two months.Morphological changes in rice roots and aerial organs were assessed alongside nitric oxide assays in rice roots,root transcriptomics,and targeted hormonomics of rice roots,leaves,and growth media.Here,we showed that co-cultivation with actively growing A.filiculoides alters rice root architecture by inducing a nitric oxide boost and accelerates leaf and tiller differentiation and proliferation.Overall,this study provides an in-depth analysis of the morphogenetic effects of co-cultivated A.filiculoides on rice during early vegetative growth.It also paves the way for studies assessing whether A.filiculoides co-cultivation primes rice plants to better withstand abiotic and biotic stresses.
基金Project supported by ClassⅢPeak Discipline of Shanghai-Materials Science and Engineering(High-Energy Beam Intelligent Processing and Green Manufacturing),China。
文摘High-entropy alloy composites(HEACs)have attracted significant attention due to their exceptional mechanical properties and chemical stability.By adjusting the content of reinforcing particles in the high-entropy alloy and by employing advanced additive manufacturing techniques,high-performance HEACs can be fabricated.However,there is still considerable room for improvement in their performance.In this study,CoCrFeMnNi HEA powders were used as the matrix,and NiCoFeAlTi high-entropy intermetallic powders were used as the high-entropy reinforcement(HER).CoCrFeMnNi/NiCoFeAlTi HEACs were fabricated using selective laser melting technology.The study results indicate that after aging,the microstructure of HEACs with HER exhibits Al-and Ti-rich nano-oxide precipitates with an orthorhombic CMCM type structure system.After aging at 873 K for 2 h,HEACs with HER achieved excellent overall mechanical properties,with an ultimate tensile strength of 731 MPa.This is attributed to the combined and synergistic effects of precipitation strengthening,dislocation strengthening,and the high lattice distortion caused by high intragranular defects,which provide a multi-scale strengthening and hardening mechanism for the plastic deformation of HEACs with HER.This study demonstrates that aging plays a crucial role in controlling the precipitate phases in complex multi-element alloys.
基金supported by Research institute/Center Supporting Program(RICSP-25-3),King Saud University,Riyadh,Saudi Arabia.
文摘TheTragopogon dubius is traditionally used to treatmany ailments,consumed as a vegetable,and utilized as fodder for livestock.Tragopogon dubius,found in the Kashmir Himalayas,is the least explored for its bioactivity properties and has a unique geographical location.This study is the first attempt to investigate the antioxidant,anticancer,and genoprotective properties of the aqueous extracts from the leaves(AQ-TrDL)and stems(AQ-TrDS)of this plant.AQ-TrDL and AQ-TrDS demonstrated significant amounts of phenolic and flavonoid contents.GC-HRMS identified various phytochemicals belonging to different classes,like carboxylic acids,fatty acid derivatives,phenols,and triterpenoids.DPPH,Superoxide,FRAP,and ABTS antioxidant assays showed that AQ-TrDS exhibited stronger radical scavenging activities than AQ-TrDL,with IC_(50)values ranging from 40.31 to 73.58μg/mL.Cytotoxicity tests revealed that AQ-TrDS significantly inhibited the growth of cancer cells inMCF-7,HCT-116,HeLa,and A-549 cell lines,with over 50%inhibition observed at concentrations ranging from 56.62 to 98.32μg/mL.Importantly,minimal effects were seen in normal fibroblast L-929 cells,with GI50 values over 434μg/mL.Additionally,genoprotective tests showed that AQ-TrDS effectively reduced“H_2)O_(2)”-induced DNA damage in lymphocytes,decreasing damage by up to 61.18%at a concentration of 320μg/mL.HPLC analysis of amino acids identified 10 amino acids in T.dubius leaves and 14 in stems,showing its nutritional value.Overall,these findings highlight the biomedical potential of T.dubius aqueous extracts for developing new pharmaceutical agents.
基金supported by the Major Special Science and Technology Plan(202302AA310020)the National Natural Science Foundation of China(NSFC)(32072925,32473087)the National Student Innovation and Entrepreneurship Training Program of Huazhong Agricultural University(202310504018)。
文摘Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry.The existing management practices are insufficient to fully prevent heat stress with an urgent need to develop preventive medicines.The aim of this study was to develop an antiheat stress Chinese herbal formula(CHF)via big data analysis techniques and to evaluate its anti-heat stress effect and mechanism of action via pharmacodynamic evaluation and network pharmacology analysis.Many anti-heat stress CHFs were collected from the Chinese National Knowledge Infrastructure(CNKI)database.Three alternative CHFs were obtained via unsupervised entropy hierarchical clustering analysis,and the most effective CHF against heat stress,Shidi Jieshu decoction(SJD),was obtained by screening in a mouse heat stress model.In dry and hot environments,SJD significantly improved the heat tolerance of AA broilers by 4-6℃.In a humid and hot environment,pretreatment with 2%SJD resulted in 100%survival of Wenchang chickens at high temperatures.The main active ingredients of SJD were identified as muntjacoside E,timosaponin C,macrostemonoside H and mangiferin via ultraperformance liquid chromatography/mass spectrometry(UPLC/MS)and database comparison.The active ingredients of SJD were found to target tumor necrosis factor-α(TNF-α),signal transducer activator of transcription 3(STAT3)and epidermal growth factor receptor(EGFR).Finally,the safety of the new formulation was assessed in an acute oral toxicity study in rats.The SJDs developed in this study provide a new option for the prevention of heat stress in animal husbandry and offer new insights for further research on anti-heat stress.
文摘Despite their biodegradability and economic advantage, plant leaves used as packaging can constitute a public health problem. The aim of this study was to characterize the microbial diversity contaminating plant leaves used as food packaging. In total, two hundred and forty (240) samples composed of Thaumatococcus daniellii and Musa paradisiaca leaves were collected and analyzed. Microbial diversity was assessed using specific medium and biochemical tests. The resistance profile was determined by the Müeller-Hinton agar diffusion method. The resistance (blaSHV, blaIMP, blaTEM) and biofilm formation (pslA, pelA) genes were searched by PCR method. Plant leaves were contaminated by bacterial (68.7%) and fungal (100%) strains. Extreme bacterial (7.1 log10 cfu/cm2) and fungal (3.5 log10 cfu/cm2) loads were obtained on Thaumatococcus daniellii leaves. Bacterial prevalence was 45.1% (S. aureus), 38.8% (E. coli) and 16.1 (P. aeruginosa). In order of decreasing importance, the prevalence of fungal species was 41.1% (A. flavus), 33.1% (A. fumigattus), 13.7% (A. niger) and 12.1% Candida sp. Resistance of E. coli to penicillins ranges from 31.6% to 87.3% and to cephalosporins from 13.3% to 28%. The P. aeruginosa strains were mainly resistant to aztreonam (87.6%). Those of S. aureus showed resistance to tetracycline (67.6), vancomycin (53), erythromycin (44.6) and levofloxacin (32.7). The blaSHV (14.28% to 18.60%) and blaIMP (9.52% to 16.28%) genes were detected in the bacterial strains. P. aeruginosa strains (19.05%) harbored the pslA and pelA genes. The health safety of these biodegradable plant-based packaging contributes to their valorization.
基金supported by the Kunlun Mountain Scholar Project of Qinghai Province,China(Project No.:2021-13).
文摘Diabetes,a metabolic disease stemming from impaired or defective insulin secretion,ranks among the most severe chronic illnesses globally.While several approved drugs exist for its treatment,they often come with multiple side effects.Therefore,there is a pressing need for safe and effective anti-diabetic medications.Traditional Chinese medicine has recognized Lycium barbarum(LB;goji berry)plant,commonly known as“wolfberry fruit”in China,for over 2,000 years.Natural compounds derived from LB show promise in reducing diabetes levels.Although research on the impact of LB on diabetes is still limited,our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved.LB can modulate diabetes through various pathways,such as inhibitingα-amylase andα-glucosidase activities,promotingβ-cell proliferation,stimulating insulin secretion,inhibiting glucagon secretion,improving insulin resistance and glucose tolerance,and enhancing antioxidant and anti-inflammatory activities.Additionally,LB improves gut flora and immunomodulation,further aiding diabetes management.These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.
基金funded by research grants from the Malacological Society of London and the Melbourne Research Scholarship for ZYCthe Hungarian Research Fund(OTKA FK 135262)the Bolyai Research Scholarship of the Hungarian Academy of Sciences for BPG。
文摘Dentisphaera Páll-Gergely&Jochum,2017 is a troglobitic land snails genus known to harbour only one species found in a single cave in North Vietnam.Based on recently collected specimens from China,three species,Dentisphaera lagredeae Chen,Grego&Páll-Gergely,sp.nov.,Dentisphaera shzha Chen,Grego&Páll-Gergely,sp.nov.and Dentisphaera zhoui Chen,Lin&Páll-Gergely,sp.nov.are introduced as new to science.The distribution range of Dentisphaera is extended based on the collecting records of these new species.
文摘In aquaculture, feed represents the main component of production costs, and the development of this sector depends on the development of an economical feed formulation that meets the qualitative and quantitative requirements of fish. The aim of this study was to determine the nutritive and microbiological quality of fish feed formulated from local flours enriched with Hermetia illucens larvae. The raw materials used for formulation were fishmeal, corn meal, low-grade rice, soybean meal and Hermetia illucens larvae meal. Different iso-protein feed compositions were prepared with 0%, 10%, 25%, 35%, 50%, 65%, 75% and 100% incorporation of Hermetia illucens larvae meal as a substitute for fish meal. Biochemical and microbiological analyses of these flours were determined using standard methods. The results showed that incorporation of larvae meal had an influence on the biochemical characteristics ash (8.15 to 20.27%), lipid (11.55 to 24.94%), fiber (13.93 to 20.41%) and dry matter (89.65 to 91.19%) of various formulated feed. Loads of fecal Streptococci, Staphylococci, Aeromonas, yeasts and molds ranged from 2.4 to 4.9 log 10 CFU/g;3.6 to 3.9 log 10 CFU/g;2.2 to 2.7 log 10 CFU/g;2.1 to 2.3 log 10 CFU/g, respectively. The level of contamination of these flours was below the microbiological criteria applicable to animal feed. Feed formulated with 0% and 10% Hermetia illucens larvae showed the best nutritive and microbiological characteristics. These results suggest that flours enriched with Hermetia illucens larvae could be used in fish feed.
文摘The literature on multi-attribute optimization for renewable energy source(RES)placement in deregulated power markets is extensive and diverse in methodology.This study focuses on the most relevant publications directly addressing the research problem at hand.Similarly,while the body of work on optimal location and sizing of renewable energy generators(REGs)in balanced distribution systems is substantial,only the most pertinent sources are cited,aligning closely with the study’s objective function.A comprehensive literature review reveals several key research areas:RES integration,RES-related optimization techniques,strategic placement of wind and solar generation,and RES promotion in deregulated powermarkets,particularly within transmission systems.Furthermore,the optimal location and sizing of REGs in both balanced and unbalanced distribution systems have been extensively studied.RESs demonstrate significant potential for standalone applications in remote areas lacking conventional transmission and distribution infrastructure.Also presents a thorough review of current modeling and optimization approaches for RES-based distribution system location and sizing.Additionally,it examines the optimal positioning,sizing,and performance of hybrid and standalone renewable energy systems.This paper provides a comprehensive review of current modeling and optimization approaches for the location and sizing of Renewable Energy Sources(RESs)in distribution systems,focusing on both balanced and unbalanced networks.
基金supported by the Department of Biotechnology(DBT),Government of India(BT/556/NE/U-Excel/).
文摘The extensive heterogeneity and the limited availability of effective targeted therapies contribute to the challenging prognosis and restricted survival observed in triple-negative breast cancer(TNBC).Recent research indicates the aberrant expression of diverse tyrosine kinases(TKs)within this cancer,contributing significantly to tumor cell proliferation,survival,invasion,and migration.The contemporary paradigm shift towards precision medicine has highlighted TKs and their receptors as promising targets for pharmacotherapy against a range of malignancies,given their pivotal roles in tumor initiation,progression,and advancement.Intensive investigations have focused on various monoclonal antibodies(mAbs)and small molecule inhibitors that specifically target proteins such as epidermal growth factor receptor(EGFR),vascular endothelial growth factor(VEGF),vascular endothelial growth factor receptor(VEGFR),cellular mesenchymal-epithelial transition factor(c-MET),human epidermal growth factor receptor 2(HER2),among others,for combating TNBC.These agents have been studied both in monotherapy and in combination with other chemotherapeutic agents.Despite these advances,a substantial terrain of unexplored potential lies within the realm of TK-targeted therapeutics,which hold promise in reshaping the therapeutic landscape.This review summarizes the various TK-targeted therapeutics that have undergone scrutiny as potential therapeutic interventions for TNBC,dissecting the outcomes and revelations stemming from diverse clinical investigations.A key conclusion from the umbrella clinical trials evidences the necessity for in-depth molecular characterization of TNBC for the maximum efficiency of TK-targeted therapeutics,either as standalone treatments or a combination.Moreover,our observation highlights that the outcomes of TK-targeted therapeutics in TNBC are substantially influenced by the diversity of the patient cohort,emphasizing the prioritization of individual patient genetic/molecular profiles for precise TNBC patient stratification for clinical studies.
基金the Higher Education Commission,Islamabad,Pakistan(No.9447/Sindh/NRPU/R&D/HEC/2017)Aga Khan University Dean's Startup Fund,Role of Natural Remedies on Psychoneurological Deficits in Murine Model as Preclinical Studies Associated with or without Diabetes(2017-2021)。
文摘OBJECTIVE:To explore the potential of combining natural herbs like chamomile and saffron for the management of anxiety and depression.METHODS:A rodent model of Major Depressive Disorder(MDD)and anxiety,secondary to streptozotocin-induced diabetes mellitus was made.A total of 6 rat groups were chosen;healthy and diseased controls;and diseased test groups of fluoxetine,saffron,chamomile,and combined saffron and chamomile treated(n=6/group).Activity by forced swim test(FST),elevated plus maze test(EPMT),and correlations with biochemical markers like serum glucose,tryptophan,C-reactive protein(CRP),brain derived neurotrophic factor(BDNF)and 5-hydroxytryptamine 2C receptor(5HT2CR)expression,were assessed at the end of the 3rd week of the treatment.A one-way analysis of variance with a post-hoc Tukey's test was applied.RESULTS:The combined herbal treatment group showed significantly better(P<0.05)than all other groups in terms of anti-hyperglycemic effect.All treatments improved the CRP levels;however,the combination group was also significantly better than fluoxetine and the individual herb groups.Only the herb groups showed efficacy in the FST with added benefits of the combination group over the healthy controls and similar trends in the EPMT.However,expression of 5HT2CR was repressed while BDNF was elevated through treatment.CONCLUSION:This study shows that in comparison to treatment with a SSRI,and individual herbs,the combination of chamomile and saffron showed overall improved outcomes.
基金supported by BT/556/NE/U-Excel/2016 grant awarded to ABKThe authors extend their appreciation to the Deanship of Research and Graduate Studies at King Khalid University for funding this work through Large Research Project under grant number RGP2/485/45.
文摘Nuclear receptors(NRs)function as crucial transcription factors in orchestrating essential functions within the realms of development,host defense,and homeostasis of body.NRs have garnered increased attention due to their potential as therapeutic targets,with drugs directed at NRs demonstrating significant efficacy in impeding chronic disease progression.Consequently,these pharmacological agents hold promise for the treatment and management of various diseases.Accumulating evidence emphasizes the regulatory role of exosome-derived microRNAs(miRNAs)in chronic inflammation,disease progression,and therapy resistance,primarily by modulating transcription factors,particularly NRs.By exploiting inflammatory pathways such as protein kinase B(Akt)/mammalian target of rapamycin(mTOR),nuclear factor kappa-B(NF-κB),signal transducer and activator of transcription 3(STAT3),and Wnt/β-catenin signaling,exosomes and NRs play a pivotal role in the panorama of development,physiology,and pathology.The internalization of exosomes modulates NRs and initiates diverse autocrine or paracrine signaling cascades,influencing various processes in recipient cells such as survival,proliferation,differentiation,metabolism,and cellular defense mechanisms.This comprehensive review meticulously examines the involvement of exosome-mediated NRs regulation in the pathogenesis of chronic ailments,including atherosclerosis,cancer,diabetes,liver diseases,and respiratory conditions.Additionally,it elucidates the molecular intricacies of exosome-mediated communication between host and recipient cells via NRs,leading to immunomodulation.Furthermore,it outlines the implications of exosome-modulated NR pathways in the prophylaxis of chronic inflammation,delineates current limitations,and provides insights into future perspectives.This review also presents existing evidence on the role of exosomes and their components in the emergence of therapeutic resistance.
文摘MicroRNAs(miRNAs) are pervasively expressed and regulate most biological functions. They function by modulating transcriptional and translational programs and therefore they orchestrate both physiological and pathological processes, such as development, cell differentiation, proliferation, apoptosis and tumor growth. miRNAs work as small guide molecules in RNA silencing, by negatively regulating the expression of several genes both at mRNA and protein level, by degrading their mRNA target and/or by silencing translation. One of the most recent advances in the field is the comprehension of their role in oncogenesis. The number of miRNA genes is increasing and an alteration in the level of miRNAs is involved in the initiation, progression and metastases formation of several tumors. Some tumor types show a distinct miRNA signature that distinguishes them from normal tissues and from other cancer types. Genetic and biochemical evidence supports the essential role of miRNAs in tumor development. Although the abnormal expression of miRNAs in cancer cells is a widely accepted phenomenon, the cause of this dysregulation is still unknown. Here, we discuss the biogenesis of miRNAs, focusing on the mechanisms by which they regulate protein synthesis. In addition we debate on their role in cancer, highlighting their potential to become therapeutic targets.
文摘AIM： To evaluate the ability of Curcuma Ionga （CL） and Tinospora cordifolia （TC） formulation to prevent anti-tuberculosis （TB） treatment （ATT） induced hepatotoxicity. METHODS： Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched （25%） CL and a hydro-ethanolic extract enriched （50%） TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS： Incidence and severity of hepatotoxicity was significantly lower in trial group （incidence： 27/192 vs 2/316, P 〈 0.0001）. Mean aspartate transaminase （AST） （195.93 ± 108.74 vs 85 ± 4.24, P 〈 0.0001）, alanine transaminase （ALT） （75.74 ± 26.54 vs 41 ± 1.41, P 〈 0.0001） and serum bilirubin （5.4 ±3.38 vs 1.5 ±0.42, P 〈 0.0001）. A lesser sputum positivity ratio at the end of 4 wk （10/67 vs 4/137, P = 0.0068） and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment （9/152 vs 2/278, P = 0.0037） was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group （P 〈 0.0001）. CONCLUSION： The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.
基金Supported by The Finnish Funding Agency for Technology and Innovation (Tekes grant No 40039/03)the Finnish Graduate School on Applied Biosciences and the Centre of Excellence on Microbial Food Safety Research,Academy of Finland
文摘AIM:To investigate the correlations between selfreported symptoms of irritable bowel syndrome(IBS) and the gastrointestinal(GI) microbiota composition.METHODS:Fecal samples were collected from a total of 44 subjects diagnosed with IBS.Their symptoms were monitored with a validated inflammatory bowel disease questionnaire adjusted for IBS patients.Thirteen quantitative real-time polymerase chain reaction assays were applied to evaluate the GI microbiota composition.Eubacteria and GI bacterial genera(Bifidobacterium,Lactobacillus and Veillonella),groups(Clostridium coccoides/Eubacterium rectale,Desulfovibrio desulfuricans) and distinct bacterial phylotypes [closest 16S rDNA sequence resemblance to species Bifidobacterium catenulatum,Clostridium cocleatum,Collinsella aerofaciens(C.aerofaciens),Coprococcus eutactus(C.eutactus),Ruminococcus torques and Streptococcus bovis ] with a suspected association with IBS were quantified.Correlations between quantities or presence/absence data of selected bacterial groups or phylotypes and various IBSrelated symptoms were investigated.RESULTS:Associations were observed between subjects' self-reported symptoms and the presence or quantities of certain GI bacteria.A Ruminococcus torques(R.torques)-like(94% similarity in 16S rRNA gene sequence) phylotype was associated with severity of bowel symptoms.Furthermore,among IBS subjects with R.torques 94% detected,the amounts of C.cocleatum 88%,C.aerofaciens-like and C.eutactus 97% phylotypes were significantly reduced.Interesting observations were also made concerning the effect of a subject's weight on GI microbiota with regard to C.aerofaciens like phylotype,Bifidobacterium spp.and Lactobacillus spp.CONCLUSION:Bacteria seemingly affecting the symptom scores are unlikely to be the underlying cause or cure of IBS,but they may serve as biomarkers of the condition.
基金supported financially by Department of Science and Technology, New Delhi, India under the SERC-DST fasttrack scheme.
文摘Plants have been used as good bio-indicators and genetic toxicity of environmental pollution in recent years. In this study, aquatic plants Hydrilla verticillata and Ceratophyllum demersum treated with 10umol/L Cd, 5 umol/L Hg, and 20 umol/L Cu for 96 h, showed changes in chlorophyll, protein content, and in DNA profiles. The changes in DNA profiles included variation in band intensity, presence or absence of certain bands and even appearance of new bands. Genomic template stability test performed for the qualitative measurement of changes in randomly amplified polymorphic DNA （RAPD） profiles, showed significant effect at the given concentration of metals. Cloning and sequencing of bands suggested that these markers although may not be homologous to any known gene but its conversion as a sequence characterized amplified region （SCAR） marker is useful in detecting the effects of genotoxin agents.
