One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despit...One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.展开更多
Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disea...Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.展开更多
Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is ma...Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.展开更多
Dear Editor,Obesity has nowadays become a global public health challenge due to its rapidly growing prevalence and interconnection with a wide spectrum of comorbidities.
The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic s...The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic substances by highly specialized cells. So, they are the target organs of sodium fluoride toxicity. The aim of this review is to highlight on hepatorenal oxidative stress and pathophysiological changes induced by treatment of experimental animals with sodium fluoride. Our review shows fluoride toxicosis caused an elevation in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, acid phosphatase, and the level of total bilirubin, and reduction in the serum levels of total protein, albumin, and globulins, and serious histopathological changes in the hepaic tissues. Also, NaF administration caused increases in serum urea, creatinine, uric acid, sodium ions, and chloride ions levels and serious histopathological changes in the kidney tissues. Treatment of experimental animals with NaF induced oxidative stress in hepatic and renal tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatorenal histopathological changes, and disturbance in liver and kidney functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver and kidney.展开更多
Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exer...Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exert diverse effects on health and disease.Obesity is a complex condition influenced by multiple interconnected factors,and the specific mechanisms linking obesity to AF may vary among individuals.Obesity contributes to the development of atrial arrhythmia.Moreover,obesity plays major roles in the pathophysiology of AF and its associated complications by inducing systemic changes,including altered hemodynamics,heightened sympathetic tone,and a persistent low-grade inflammatory state.Although the associations between overweight or obesity and elevated risk of AF have been established,the underlying mechanisms remain incompletely characterized.This article highlights the pathophysiological aspects of adipokines,such as Angiopoietin-like protein 2,Fibroblast growth factor 21,Lipocalin,Vaspin,Visfatin,and Nesfatin-1,in AF and concludes that adipokines play major roles in AF pathogenesis.展开更多
Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation o...Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation of foveolar cells accompanied by their increased exfoliation, and they are macroscopically indistinguishable from other polyps with lower or higher malignant potential. Panendoscopy allows detection and differentiation of gastric polyps, usually after obtaining histopathological biopsy specimens. Unremoved gastric hyperplastic polyps may enlarge and sometimes spontaneously undergo a sequential progression to cancer. For this reason, gastric hyperplastic polyps larger than 5 mm in size should be removed in one piece. After excision of polyps with atypical focal lesion, endoscopic surveillance is suggested depending on histopathological diagnosis and possibility of confirming the completeness of endoscopic resection. Because of the risk of cancer development also in gastric mucosa outside the polyp, neighboring fragments of gastric mucosa should undergo microscopic investigations. This procedure allows for identification of patients who can benefit most from oncological endoscopic surveillance. If Helicobacter pylori(H. pylori) infection of the gastric mucosa is confirmed, treatment strategies should include eradication of bacteria, which may prevent progression of intestinal metaplasia. The efficacy of H. pylori eradication should be checked 3-6 mo later.展开更多
AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grow...AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.展开更多
Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects o...Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.展开更多
AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chron...AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t tests were used. P < 0.05 was deemed statistically significant. RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 ± 26.32 cm 3 , n = 12, vs 53.19 ± 33.80 cm 3 , n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm 3 vs 6.77 ± 15.75 cm 3 , P < 0.0001)/(34.6% ± 10.6%, n = 65, vs 53.3% ± 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.展开更多
Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI ...Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI in treating allergic rhinitis, asthma or allergy to the venom of Hymenoptera insects. It has also been proven that administration of increasing preparation doses of allergen extractions alleviates the symptoms in patients after the exposure to some sensitizing allergens. The effect of the AI remains visible many years after completion of the therapy. Studies have been done in an attempt to employ specific immunotherapy in patients with food allergy symptoms. They have been mostly concerned with populations of patients suffering from allergy to the protein found in cow’s milk and hen eggs. It appears that a need arises to create a new therapeutic method for successful treatment of food allergies and specific allergen immunotherapy seems to be a promising step. Although still in its experimental phase, in many well documented cases the method allows for building patient’s tolerance towards small doses of sensitizing allergen and seems conducive to protecting the patient from anaphylactic reactions after incidental allergen consumption.展开更多
Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unp...Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unpleasant side effects.Therefore,it is essential to understand the mechanism of migraine to develop potential preventive and therapeutic agents.Studies have confirmed that traditional Chinese medicine(TCM)can alleviate migraine by reducing neuroinflammation,oxidative stress,and apoptosis and regulating neurotransmitters and vascular function.Starting from the pathophysiological process of migraine,this review summarizes the mechanisms by which TCM improves neurovascular function after migraine to provide clues and a reference for the clinical application of TCM in the prevention and treatment of migraine and guide further research and development of new drugs.展开更多
Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fun...Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.展开更多
Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen...Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.展开更多
The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation s...The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD,which belonged to the concept of "toxin" in Traditional Chinese medicines(TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology,platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance,inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.展开更多
Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to man...Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to many other diseases.Current research shows that patients with hypopituitarism have a high risk of developing NAFLD.After the adenohypophysis is dominated by hypothalamic hormones,hormones are secreted to act on the corresponding tissues or organs.It is characterized by a decrease in the thyroid hormone,cortisol,and growth hormone levels.In this review,we analyzed the mechanisms related to NAFLD through thyroid secretion,growth hormone secretion,sex hormone,and prolactin axes in patients with hypopituitarism,which will provide information and a theoretical basis for clinical diagnosis and treatment.展开更多
The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular rec...The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.展开更多
Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articul...Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.展开更多
Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathop...Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.展开更多
文摘One of the main causes of cancer-related morbidity and mortality globally is hepatocellular carcinoma(HCC).At every stage of the disease,HCC may now be treated using a variety of therapy techniques.Nevertheless,despite the abundance of effective therapeutic choices,the prognosis for patients with HCC is still typically dismal.Prognostic indicators are crucial when assessing prognosis and tracking tumor metastases or recurrence.There are many prognostic markers in HCC.We mainly focused on newly reported prognostic markers such as MEX3A,apolipoprotein B,alpha-fetoprotein,circulating tumor cells,SAMD13,Agrin,and Glypican-3 in the pathogenesis of HCC.Further,we highlighted how these prognostic markers correlated to clinical parameters such as tumor node metastasis,tumor diameter,differentiation,hepatocirrhosis,vascular invasion,and others in HCC.Therefore,identifying specific prognostic biomarkers of HCC helps to provide a great opportunity to improve the prognosis in patients with HCC and provide therapeutic targets.
文摘Liver fibrosis is a complex pathological process controlled by a variety of cells,mediators and signaling pathways.Hepatic stellate cells play a central role in the development of liver fibrosis.In chronic liver disease,hepatic stellate cells undergo dramatic phenotypic activation and acquire fibrogenic properties.This review focuses on the pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis.They enter the cell cycle under the influence of various triggers.The“Initiation”phase of hepatic stellate cells activation overlaps and continues with the“Perpetuation”phase,which is characterized by a pronounced inflammatory and fibrogenic reaction.This is followed by a resolution phase if the injury subsides.Knowledge of these pathophysiological mechanisms paved the way for drugs aimed at preventing the development and progression of liver fibrosis.In this respect,impairments in intracellular signaling,epigenetic changes and cellular stress response can be the targets of therapy where the goal is to deactivate hepatic stellate cells.Potential antifibrotic therapy may focus on inducing hepatic stellate cells to return to an inactive state through cellular aging,apoptosis,and/or clearance by immune cells,and serve as potential antifibrotic therapy.It is especially important to prevent the formation of liver cirrhosis since the only radical approach to its treatment is liver transplantation which can be performed in only a limited number of countries.
基金supported by grants from the National Natural Science Foundation(81330025).
文摘Paroxysmal kinesigenic dyskinesia(PKD),the most common type of paroxysmal movement disorder,is characterized by sudden and brief attacks of choreoathetosis or dystonia triggered by sudden voluntary movements.PKD is mainly caused by mutations in the PRRT2 or TMEM151A gene.The exact pathophysiological mechanisms of PKD remain unclear,although the function of PRRT2 protein has been well characterized in the last decade.Based on abnormal ion channels and disturbed synaptic transmission in the absence of PRRT2,PKD may be channelopathy or synaptopathy,or both.In addition,the cerebellum is regarded as the key pathogenic area.Spreading depolarization in the cerebellum is tightly associated with dyskinetic episodes.Whereas,in PKD,other than the cerebellum,the role of the cerebrum including the cortex and thalamus needs to be further investigated.
文摘Dear Editor,Obesity has nowadays become a global public health challenge due to its rapidly growing prevalence and interconnection with a wide spectrum of comorbidities.
文摘The liver is a primary site for xenobiotics detoxification, and its metabolism is readily altered by toxicity. The kidney is a common target for toxic xenobiotics due to its capacity to extract and concentrate toxic substances by highly specialized cells. So, they are the target organs of sodium fluoride toxicity. The aim of this review is to highlight on hepatorenal oxidative stress and pathophysiological changes induced by treatment of experimental animals with sodium fluoride. Our review shows fluoride toxicosis caused an elevation in the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, acid phosphatase, and the level of total bilirubin, and reduction in the serum levels of total protein, albumin, and globulins, and serious histopathological changes in the hepaic tissues. Also, NaF administration caused increases in serum urea, creatinine, uric acid, sodium ions, and chloride ions levels and serious histopathological changes in the kidney tissues. Treatment of experimental animals with NaF induced oxidative stress in hepatic and renal tissues. It can be concluded that administration of sodium fluoride to experimental animals induced oxidative stress, serious hepatorenal histopathological changes, and disturbance in liver and kidney functions. So, human should be advised to decrease exposure to sodium fluoride to decrease the harmful effects of NaF on liver and kidney.
文摘Atrial fibrillation(AF)is a prevalent cardiac arrhythmia characterized by irregular and frequently rapid electrical activity in the atria.Adipokines are bioactive molecules that are secreted by adipose tissue,and exert diverse effects on health and disease.Obesity is a complex condition influenced by multiple interconnected factors,and the specific mechanisms linking obesity to AF may vary among individuals.Obesity contributes to the development of atrial arrhythmia.Moreover,obesity plays major roles in the pathophysiology of AF and its associated complications by inducing systemic changes,including altered hemodynamics,heightened sympathetic tone,and a persistent low-grade inflammatory state.Although the associations between overweight or obesity and elevated risk of AF have been established,the underlying mechanisms remain incompletely characterized.This article highlights the pathophysiological aspects of adipokines,such as Angiopoietin-like protein 2,Fibroblast growth factor 21,Lipocalin,Vaspin,Visfatin,and Nesfatin-1,in AF and concludes that adipokines play major roles in AF pathogenesis.
文摘Gastric polyps become a major clinical problem because of high prevalence and tendency to malignant transformation of some of them. The development of gastric hyperplastic polyps results from excessive proliferation of foveolar cells accompanied by their increased exfoliation, and they are macroscopically indistinguishable from other polyps with lower or higher malignant potential. Panendoscopy allows detection and differentiation of gastric polyps, usually after obtaining histopathological biopsy specimens. Unremoved gastric hyperplastic polyps may enlarge and sometimes spontaneously undergo a sequential progression to cancer. For this reason, gastric hyperplastic polyps larger than 5 mm in size should be removed in one piece. After excision of polyps with atypical focal lesion, endoscopic surveillance is suggested depending on histopathological diagnosis and possibility of confirming the completeness of endoscopic resection. Because of the risk of cancer development also in gastric mucosa outside the polyp, neighboring fragments of gastric mucosa should undergo microscopic investigations. This procedure allows for identification of patients who can benefit most from oncological endoscopic surveillance. If Helicobacter pylori(H. pylori) infection of the gastric mucosa is confirmed, treatment strategies should include eradication of bacteria, which may prevent progression of intestinal metaplasia. The efficacy of H. pylori eradication should be checked 3-6 mo later.
文摘AIM: To explore the approaches exerted by mesenchymal stem cells (MSCs) to improve Parkinson’s disease (PD) pathophysiology.METHODS: MSCs were harvested from bone marrow of femoral bones of male rats, grown and propagated in culture. Twenty four ovariectomized animals were classified into 3 groups: Group (1) was control, Groups (2) and (3) were subcutaneously administered with rotenone for 14 d after one month of ovariectomy for induction of PD. Then, Group (2) was left untreated, while Group (3) was treated with single intravenous dose of bone marrow derived MSCs (BM-MSCs). SRY gene was assessed by PCR in brain tissue of the female rats. Serum transforming growth factor beta-1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1) and brain derived neurotrophic factor (BDNF) levels were assayed by ELISA. Brain dopamine DA level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) and nestin gene expression were detected by semi-quantitative real time PCR. Brain survivin expression was determined by immunohistochemical procedure. Histopathological investigation of brain tissues was also done.RESULTS: BM-MSCs were able to home at the injured brains and elicited significant decrease in serum TGF-β1 (489.7 ± 13.0 vs 691.2 ± 8.0, P < 0.05) and MCP-1 (89.6 ± 2.0 vs 112.1 ± 1.9, P < 0.05) levels associated with significant increase in serum BDNF (3663 ± 17.8 vs 2905 ± 72.9, P < 0.05) and brain DA (874 ± 15.0 vs 599 ± 9.8, P < 0.05) levels as well as brain TH (1.18 ± 0.004 vs 0.54 ± 0.009, P < 0.05) and nestin (1.29 ± 0.005 vs 0.67 ± 0.006, P < 0.05) genes expression levels. In addition to, producing insignificant increase in the number of positive cells for survivin (293.2 ± 15.9 vs 271.5 ± 15.9, P > 0.05) expression. Finally, the brain sections showed intact histological structure of the striatum as a result of treatment with BM-MSCs.CONCLUSION: The current study sheds light on the therapeutic potential of BM-MSCs against PD pathophysiology via multi-mechanistic actions.
基金Tianjin Municipal Education Commission Scientific Research Program,China,No.2022KJ271。
文摘Obstructive jaundice(OJ)is a common problem in daily clinical practice.However,completely understanding the pathophysiological changes in OJ remains a challenge for planning current and future management.The effects of OJ are widespread,affecting the biliary tree,hepatic cells,liver function,and causing systemic complications.The lack of bile in the intestine,destruction of the intestinal mucosal barrier,and increased absorption of endotoxins can lead to endotoxemia,production of proinflammatory cytokines,and induce systemic inflammatory response syndrome,ultimately leading to multiple organ dysfunction syndrome.Proper management of OJ includes adequate water supply and electrolyte replacement,nutritional support,preventive antibiotics,pain relief,and itching relief.The surgical treatment of OJ depends on the cause,location,and severity of the obstruction.Biliary drainage,surgery,and endoscopic intervention are potential treatment options depending on the patient's condition.In addition to modern medical treatments,Traditional Chinese medicine may offer therapeutic benefits for OJ.A comprehensive search was conducted on PubMed for relevant articles published up to August 1970.This review discusses in detail the pathophysiological changes associated with OJ and presents effective strategies for managing the condition.
基金Supported by Grants from Chung Shan Medical University with Grant Numbers CSMUTTM-097-001 and CSMU-TTM-098-002
文摘AIM: To study the pathophysiological significance of gallbladder volume (GBV) and ejection fraction changes in gallstone patients.METHODS: The fasting GBV of gallstone patients with acute cholecystitis (n = 99), chronic cholecystitis (n = 85) and non-gallstone disease (n = 240) were measured by preoperative computed tomography. Direct saline injection measurements of GBV after cholecystectomy were also performed. The fasting and postprandial GBV of 65 patients with gallstones and chronic cholecystitis and 53 healthy subjects who received health examinations were measured by abdominal ultrasonography. Proper adjustments were made after the correction factors were calculated by comparing the preoperative and postoperative measurements. Pathological correlations between gallbladder changes in patients with acute calculous cholecystitis and the stages defined by the Tokyo International Consensus Meeting in 2007 were made. Unpaired Student's t tests were used. P < 0.05 was deemed statistically significant. RESULTS: The fasting GBV was larger in late stage than in early/second stage acute cholecystitis gallbladders (84.66 ± 26.32 cm 3 , n = 12, vs 53.19 ± 33.80 cm 3 , n = 87, P = 0.002). The fasting volume/ejection fraction of gallbladders in chronic cholecystitis were larger/lower than those of normal subjects (28.77 ± 15.00 cm 3 vs 6.77 ± 15.75 cm 3 , P < 0.0001)/(34.6% ± 10.6%, n = 65, vs 53.3% ± 24.9%, n = 53, P < 0.0001). CONCLUSION: GBV increases as acute cholecystitis progresses to gangrene and/or empyema. Gallstone formation is associated with poorer contractility and larger volume in gallbladders that contain stones.
文摘Apart from avoiding exposure, allergen immunotherapy (AI) is the only causal method of treating allergic diseases. The results of numerous studies have been published concerning the safety and effectiveness of the AI in treating allergic rhinitis, asthma or allergy to the venom of Hymenoptera insects. It has also been proven that administration of increasing preparation doses of allergen extractions alleviates the symptoms in patients after the exposure to some sensitizing allergens. The effect of the AI remains visible many years after completion of the therapy. Studies have been done in an attempt to employ specific immunotherapy in patients with food allergy symptoms. They have been mostly concerned with populations of patients suffering from allergy to the protein found in cow’s milk and hen eggs. It appears that a need arises to create a new therapeutic method for successful treatment of food allergies and specific allergen immunotherapy seems to be a promising step. Although still in its experimental phase, in many well documented cases the method allows for building patient’s tolerance towards small doses of sensitizing allergen and seems conducive to protecting the patient from anaphylactic reactions after incidental allergen consumption.
基金supported by the National Natural Science Foundation of China(Grant No.82004331)Key Research and Development Program of Hu Bei Province of China(2021ACA004-03 and 2022ACA003-02-002)。
文摘Migraine is a highly prevalent neurological disorder and has been the second leading cause of disability worldwide for many years.The pathophysiology of migraines is complicated,and most available medications have unpleasant side effects.Therefore,it is essential to understand the mechanism of migraine to develop potential preventive and therapeutic agents.Studies have confirmed that traditional Chinese medicine(TCM)can alleviate migraine by reducing neuroinflammation,oxidative stress,and apoptosis and regulating neurotransmitters and vascular function.Starting from the pathophysiological process of migraine,this review summarizes the mechanisms by which TCM improves neurovascular function after migraine to provide clues and a reference for the clinical application of TCM in the prevention and treatment of migraine and guide further research and development of new drugs.
基金supported by the China Postdoctoral Science Foundation,No.2022M712689the Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.22KJB1800029+1 种基金The University Student Innovation Project of Yangzhou University,No.XCX20240856The Jiangsu Provincial Science and Technology Talent Project,No.FZ20240964(all to TX).
文摘Ischemic stroke is a serious medical event that cannot be predicted in advance and can have longlasting effects on patients,families,and communities.A deeper understanding of the changes in gene expression and the fundamental molecular mechanisms involved could help address this critical issue.In recent years,research into regulatory long non-coding(lnc)RNAs,a diverse group of RNA molecules with regulatory functions,has emerged as a promising direction in the study of cerebral infarction.This review paper aims to provide a comprehensive exploration of the roles of regulatory lncRNAs in cerebral infarction,as well as potential strategies for their application in clinical settings.LncRNAs have the potential to act as“sponges”that attract specific microRNAs,thereby regulating the expression of microRNA target genes.These interactions influence various aspects of ischemic stroke,including reperfusion-induced damage,cell death,immune responses,autophagy,angiogenesis,and the generation of reactive oxygen species.We highlight several regulatory lncRNAs that have been utilized in animal model treatments,including lncRNA NKILA,lncRNA Meg8,and lncRNA H19.Additionally,we discuss lncRNAs that have been used as biomarkers for the diagnosis and prognosis of cerebral infarction,such as lncRNA FOXO3,lncRNA XIST,and lncRNA RMST.The lncRNAs hold potential for genetic-level treatments in patients.However,numerous challenges,including inefficiency,low targeting accuracy,and side effects observed in preliminary studies,indicate the need for thorough investigation.The application of lncRNAs in ischemic stroke presents challenges that require careful and extensive validation.
基金supported by the National Natural Science Foundation of China,Nos.82171387 and 31830111(both to SL).
文摘Stroke,particularly ischemic stroke,is the leading cause of long-term disability and mortality worldwide.It occurs due to the occlusion of the cerebral arteries,which significantly reduces the delivery of blood,oxygen,and essential nutrients to brain tissues.This deprivation triggers a cascade of cellular events that ultimately leads to neuronal death.Recent studies have clarified the multifactorial pathogenesis of ischemic stroke,highlighting the roles of energy failure,excitotoxicity,oxidative stress,neuroinflammation,and apoptosis.This review aimed to provide a comprehensive insight into the fundamental mechanisms driving neuronal death triggered by ischemia and to examine the progress of neuroprotective therapeutic approaches designed to mitigate neuronal loss and promote neurological recovery after a stroke.Additionally,we explored widely accepted findings regarding the potential pathways implicated in neuronal death during ischemic stroke,including the interplay of apoptosis,autophagy,pyroptosis,ferroptosis,and necrosis,which collectively influence neuronal fate.We also discussed advancements in neuroprotective therapeutics,encompassing a range of interventions from pharmacological modulation to stem cell-based therapies,aimed at reducing neuronal injury and enhancing functional recovery following ischemic stroke.Despite these advancements,challenges remain in translating mechanistic insights into effective clinical therapies.Although neuroprotective strategies have shown promise in preclinical models,their efficacy in human trials has been inconsistent,often due to the complex pathology of ischemic stroke and the timing of interventions.In conclusion,this review synthesizes mechanistic insights into the intricate interplay of molecular and cellular pathways driving neuronal death post-ischemia.It sheds light on cutting-edge advancements in potential neuroprotective therapeutics,underscores the promise of regenerative medicine,and offers a forward-looking perspective on potential clinical breakthroughs.The ongoing evolution of precision-targeted interventions is expected to significantly enhance preventative strategies and improve clinical outcomes.
基金supported by a National 973 Project(No.2015CB554405)
文摘The pathophysiological characteristics of Phlegm-stasis Cementation Syndrome in Coronary Heart Disease(CHD) has been summarized in this article. According to epidemiological investigations, phlegm-stasis cementation syndrome has become a dominant syndrome in CHD along with the improvement in living and dietary condition. The interaction between blood stasis and phlegm turbidity that is called Phlegmstasis Cementation Syndrome exists in CHD and other diseases. The bridge linked blood stasis and phlegm turbidity lies in the adversely effects of lipid metabolism disorder on platelet activation, vascular function and hemorheology indexes. Lipid metabolism disorder also can induce persistent inflammation including monocyte/macrophage activation and oxidative stress. Inflammation also is an important stimulating factor for atherosclerosis and the biology that underlies the complications of CHD,which belonged to the concept of "toxin" in Traditional Chinese medicines(TCM). On the other hand, the important function of inflammatory process on abnormal hemorheology,platelet activation and vascular dysfunction can be used to elucidate the basic pathogenetic condition of the toxin inducing blood stasis in TCM. Therefore, it is this pathological process that can be used to address the basic pathogenetic theory of phlegm turbidity inducing the symptom of toxin and blood stasis, and subsequently phlegm-stasis cementation in TCM. We deduced that lipid metabolic disturbance,inflammation activation, vascular dyfunction and hemorheological disorders could be as pathophysiological characteristics of Phlegm-stasis cementation syndrome.
文摘Nonalcoholic fatty liver disease(NAFLD)is a common chronic metabolic liver disease worldwide.It is closely related to diseases of the cardiovascular system and chronic kidney disease.It can also occur secondary to many other diseases.Current research shows that patients with hypopituitarism have a high risk of developing NAFLD.After the adenohypophysis is dominated by hypothalamic hormones,hormones are secreted to act on the corresponding tissues or organs.It is characterized by a decrease in the thyroid hormone,cortisol,and growth hormone levels.In this review,we analyzed the mechanisms related to NAFLD through thyroid secretion,growth hormone secretion,sex hormone,and prolactin axes in patients with hypopituitarism,which will provide information and a theoretical basis for clinical diagnosis and treatment.
基金supported by the National Natural Science Foundation of China,Nos.82301093(to QC)and 22334004(to HY)the Fuzhou University Fund for Testing Precious Equipment,No.2025T038(to QC)。
文摘The mechanisms underlying the pathophysiology of ischemic stroke are complex and multifactorial and include excitotoxicity,oxidative stress,inflammatory responses,and blood–brain barrier disruption.While vascular recanalization treatments such as thrombolysis and mechanical thrombectomy have achieved some success,reperfusion injury remains a significant contributor to the exacerbation of brain injury.This emphasizes the need for developing neuroprotective strategies to mitigate this type of injury.The purpose of this review was to examine the application of nanotechnology in the treatment of ischemic stroke,covering research progress in nanoparticlebased drug delivery,targeted therapy,and antioxidant and anti-inflammatory applications.Nanobased drug delivery systems offer several advantages compared to traditional therapies,including enhanced blood–brain barrier penetration,prolonged drug circulation time,improved drug stability,and targeted delivery.For example,inorganic nanoparticles,such as those based on CeO_(2),have been widely studied for their strong antioxidant capabilities.Biomimetic nanoparticles,such as those coated with cell membranes,have garnered significant attention owing to their excellent biocompatibility and targeting abilities.Nanoparticles can be used to deliver a wide range of neuroprotective agents,such as antioxidants(e.g.,edaravone),anti-inflammatory drugs(e.g.,curcumin),and neurotrophic factors.Nanotechnology significantly enhances the efficacy of these drugs while minimizing adverse reactions.Although nanotechnology has demonstrated great potential in animal studies,its clinical application still faces several challenges,including the long-term safety of nanoparticles,the feasibility of large-scale production,quality control,and the ability to predict therapeutic effects in humans.In summary,nanotechnology holds significant promise for the treatment of ischemic stroke.Future research should focus on further exploring the mechanisms of action of nanoparticles,developing multifunctional nanoparticles,and validating their safety and efficacy through rigorous clinical trials.Moreover,interdisciplinary collaboration is essential for advancing the use of nanotechnology in stroke treatment.
文摘Rheumatoid arthritis(RA)is a chronic systemic autoimmune disease that extends beyond joint inflammation,affecting pulmonary and metabolic pathways.Interstitial lung disease(ILD)is one of its most serious extra-articular complications,while type 2 diabetes mellitus(T2DM)frequently coexists with RA and may exacerbate inflammatory and fibrotic processes.This editorial discusses the study by Sutton et al,the largest population-based analysis to date exploring the link between T2DM and ILD in patients with RA,and reflects on its mechanistic and clinical implications.In a nationwide cohort of more than 120000 hospitalized RA patients,Sutton et al demonstrated that the coexistence of T2DM nearly doubles the odds of developing ILD(odds ratio=2.02;95%confidence interval:1.84-2.22),with additional increases in pulmonary hypertension,pneumothorax,and length of stay.These findings reinforce the concept of a metabolic-pulmonary-autoimmune axis,in which chronic inflammation promotes insulin resistance and metabolic dysfunction,while hyperglycaemia and advanced glycation end-products amplify oxidative stress and fibrogenesis.This reciprocal interaction may induce a self-perpetuating cycle of“metaflammation”,fibrosis,and organ damage.Conclusion:Recognizing diabetes as a silent amplifier of RA-associated ILD redefines the interface between rheumatology,pulmonology,and endocrinology.Early detection and integrated management of metabolic and pulmonary comorbidities should be prioritized,while future studies must determine whether optimizing glycemic control can attenuate pulmonary fibrosis and improve longterm outcomes.
文摘Spinal cord injury(SCI) often results in permanent dysfunction of locomotion,sensation,and autonomic regulation,imposing a substantial burden on both individuals and society(Anjum et al.,2020).SCI has a complex pathophysiology:an initial primary injury(mechanical trauma,axonal disruption,and hemorrhage) is followed by a progressive secondary injury cascade that involves ischemia,neuronal loss,and inflammation.Given the challenges in achieving regeneration of the injured spinal cord,neuroprotection has been at the forefront of clinical research.
