Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and com...Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.展开更多
Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecul...Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.展开更多
Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results ...Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results were obtained.Firstly,at pressures lower than 53GPa,the opaque minerals still keep the unmelted state,while at 78 GPa and higher,FeNi metal and troilite form eutectic intergrowths occurring as disorderly fine veinlets filling the shock-induced fractures in silicate minerals.Secondly,single kamacite grains still maintain their contour at 12 GPa,but a part of brittle troilite grains was fragmented and squeezed into the shock-induced fractures within kamacite grains.At53 and 133 GPa,many more troilite fragments are poured in the kamacite interior to form disordered hybrid aggregates or to form squiggly strips,respectively.Similar phenomena are observed within single troilite grains,but the mineral squeezed into troilite grains is kamacite.Thirdly,chromite is a hard and refractory oxide mineral.When the shock pressure rises step by step from 12 to 133 GPa,the shock effect of chromite is only fragmentation.Its grain size decreases from tens of um at 53 GPa to a few um at 133 GPa.And,fourthly,native copper exhibits distinct redistribution behavior at high temperature.In Jilin samples shock-loaded to 12 GPa,copper initially located at troilite-kamacite interfaces partially transferred into small troilite grains containing fine FeNi particles.At 53 and 133 GPa,native copper preferentially transferred into larger troilite grains containing more particles of eutectic FeNi metal.展开更多
To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was struct...To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.展开更多
The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from...The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.展开更多
Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while...Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while the potential for further vibration reduction remains debated,largely due to unclear underlying mechanisms.In light of the popularization of electronic detonators and the representativeness of double-hole configurationsfor multiple blastholes,it is essential to investigate the vibration characteristics induced by time-delayed double blastholes.Therefore,a series of doubleborehole experimental blasts was conducted in an underground roadway to clarify the variation in vibration from single-hole to dual-hole conditions.Based on the experimental data and inherent limitations,an exact full-fieldtheoretical model was further employed to systematically analyze the effects of delay time,charge length,and borehole inclination angle on vibrations induced by various doublehole configurations.The experimental data and theoretical analysis reveal that the general scaled distance effectively predicts vibrations in delayed blasting but does not reflectvibration reduction.Increasing delay time causes fluctuatingPPVs,which stabilize slightly above single-hole PPVs as delay times exceed a certain value.The delayed blasting primarily reduces near-fieldfrequencies.Longer charge lengths in double boreholes increase PPV levels and attenuation rates within a certain length,and the vibration behavior of combined long and short charge lengths is governed by the long blasthole.Larger blasthole inclination angles enhance vibration amplitude and reduce PPV attenuation rates.Optimizing inclination angles is more critical than adjusting delay times,and parallel boreholes offer the best vibration control.展开更多
Objective:To assess the effectiveness and safety of the Fuzheng Buxue Dietary Therapy(FBDT)for mitigating myelosuppression caused by chemotherapy containing platinum agents.Methods:In this non-randomized concurrent co...Objective:To assess the effectiveness and safety of the Fuzheng Buxue Dietary Therapy(FBDT)for mitigating myelosuppression caused by chemotherapy containing platinum agents.Methods:In this non-randomized concurrent controlled trial,70 chemotherapy patients were evenly divided into two groups:the FBDT group and a standard care control group.The control group adhered to the standard oncological treatment protocol.Meanwhile,the FBDT group,in addition to the standard regimen,took an additional 300ml of the formula daily with lunch,beginning one week prior to chemotherapy and lasting for two weeks.The study conducted a comprehensive comparative analysis of peripheral blood counts,Traditional Chinese Medicine(TCM)symptom scores,Karnofsky Performance Status(KPS)scores,and the incidence of adverse reactions among patients from both groups.Outcomes:A total of 64 patients completed the study,with 32 in each group.FBDT group exhibited a significantly higher white blood cells recovery level one and three weeks after the chemotherapy compared to control group(3.23±0.68 vs 2.76±0.75(×10^(9)/L);3.92±1.07 vs 3.44±0.91(×10^(9)/L);P<0.05).Furthermore,three weeks after the start of chemotherapy,FBDT group had higher platelet recovery levels than the control group(164.25±54.38 vs 124.81±47.88(×10^(9)/L),P<0.05).Additionally,the TCM syndrome scores in FBDT group were lower(P<0.05),and the KPS scores were significantly higher in FBDT group(P<0.05).No serious adverse events were observed in two groups.Conclusion:FBDT is effective and safe in reducing myelosuppression caused by platinum chemotherapy.Future study should involve larger,multicenter trials to better understand dose-response and overall therapeutic value of FBDT.展开更多
Objective: To study the effects of angiostatin (AS) gene mediated by liposome on human pancreatic cancer cell line SW1990. Methods: Angiostatin gene was cloned into the eu- karyotic expression vector pRC/CMV. The reco...Objective: To study the effects of angiostatin (AS) gene mediated by liposome on human pancreatic cancer cell line SW1990. Methods: Angiostatin gene was cloned into the eu- karyotic expression vector pRC/CMV. The recombi- nant of pRC/CMV-AS was introduced into the pan- creatic cancer cell line, SW1990. The mechanism of anti-tumor was studied and tested. Results: The eukaryotic expression vector pRC/ CMV-AS was identified by the restriction digest. pRC/CMV-AS was stably integrated into the target cells and expressed by Western blot and drug-sensi- tivity tests, and inhibited the vascular endothelial cells proliferation in vitro. In addition, the effects of the angiostatin vector on reducing the volume of tumors implanted in nude mouse models were also noted. Conclusion: This study demonstrated that the recom- binant pRC/CMV-AS mediated by liposome may play a potential role in the treatment of pancreatic cancer in the future.展开更多
Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ ...Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conven-tional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.展开更多
The liver is an exceptional organ,not only because of its unique anatomical and physiological characteristics,but also because of its unlimited regenerative capacity.Unfolding of the molecular mechanisms that govern l...The liver is an exceptional organ,not only because of its unique anatomical and physiological characteristics,but also because of its unlimited regenerative capacity.Unfolding of the molecular mechanisms that govern liver regeneration has allowed researchers to exploit them to augment liver regeneration.Dramatic progress in the field,however,was made by the introduction of the powerful tool of gene therapy.Transfer of genetic materials,such as hepatocyte growth factor,using both viral and non-viral vectors has proved to be successful in augmenting liver regeneration in various animal models.For future clinical studies,ongoing research aims at eliminating toxicity of viral vectors and increasing transduction efficiency of non-viral vectors,which are the main drawbacks of these systems.Another goal of current research is to develop gene therapy that targets specific liver cells using receptors that are unique to and highly expressed by different liver cell types.The outcome of such investigations will,undoubtedly,pave the way for future successful clinical trials.展开更多
Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adul...Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were used.They were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group C-3.S mg/kg DA and 100 mg/kg vitamin C;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin C.Croup E was left untreated.Parameters assessed include:rectal temperature,body weight changes,packed cell volume(PCV),Haemoglobin concentration(Hb),total leucocyte count(TLC) differential leucocyte count(DLC),parasitaemia,clinical signs and survivability.Results:Average pre-patent period of 5 days was recorded.Parasites in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PCV,Hb,TLC and increases in rectal temperature following infection were reversed by the treatments.The rats that received drug combinations(groups B,C and D)showed faster and higher recovery rates than the uninfected control and group A.Conclusions:Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.展开更多
This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. ...This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.展开更多
To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression...To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly展开更多
The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. Bu...The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.展开更多
AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the e...AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.展开更多
Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the G...Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods:nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results:Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). Conclusions:Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.展开更多
Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extra...Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.展开更多
Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism rem...Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.展开更多
Objectives： To assess the genotoxic effect of a new antitumor ozone-photodynamic therapy using the improvedmodification of the COMET assay. Methods： Xenograft cancer models on 58 rats were used. The sarcoma RA was t...Objectives： To assess the genotoxic effect of a new antitumor ozone-photodynamic therapy using the improvedmodification of the COMET assay. Methods： Xenograft cancer models on 58 rats were used. The sarcoma RA was transplantedsubcutaneously, and after increasing of tumor volume from 0.5 to 4.2 cm3, rats were divided into the four groups： ＂Intact＂--healthy,＂Control＂--with xenografted tumors and no treatment, ＂PDT＂--the rats treated with the photodynamic therapy, ＂PDT ＋ozone＂--the rats were treated with both photodynamic therapy and injections of ozonated saline solution. The toxicity of treatmentwas assessed by DNA damage in leukocytes using the new modification of the COMET assay. The analysis of the ＂COMETs＂ wasperformed following the percentage of DNA in the tail of the ＂COMET＂ （% TDNA）. Results： A combination of PDT and ozonemakes the strongest negative impact on tumor growth. The tumor growth inhibition is associated with low genotoxic exposure ofozone-photodynamic therapy on whole blood leukocytes of cancer rats. Conclusions： A new modification of the COMET assay canprovide the assessment of the genotoxic effect of the antitumor therapy in experimental neoplasia.展开更多
To study the therapeutic effects of herpes simplex virus thymidine kinase gene transferred by the EBV based expression vector on experimental hepatocellular carcinoma, pDR2 TK gene was delivered into human hepatoc...To study the therapeutic effects of herpes simplex virus thymidine kinase gene transferred by the EBV based expression vector on experimental hepatocellular carcinoma, pDR2 TK gene was delivered into human hepatocellular carcinoma cell line SMMC 7721 by using liposome mediated transfection technique,and then gene expression was detected by RT PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model,the antitumor effects of pDR2 TK /GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2 TK /GCV had cytotoxic effect and about 70 % SMMC 7721 cells were killed when GCV was at 1000 μmol/L. In vivo experiment showed that the tumor size in nude mice with transferred pDR2 TK gene was significantly smaller than that in control group . On the 10th day the tumor in 3 mice (60 %) disappeared completely after GCV treatment. It is concluded that the pDR2 TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.展开更多
文摘Experimental therapies targeting immune and stromal cells,such as mast cells,cancer-associated fibroblasts,dendritic cells,and tumor endothelial cells,in the treatment of gastrointestinal solid tumors pose new and complex surgical and medico-legal challenges.These innovative treatments require that informed consent not be limited to simple acceptance of the medical procedure,but instead reflect a true relational and cognitive process grounded in understanding,free choice,and the ability to revoke consent at any time.In particular,it is essential that the patient understands the experimental nature of the therapy,its development stage,potential benefits and risks,as well as the implications for their health and personal dignity.In the case of stromal cell-based treatments,which may exert complex immunomodulatory effects or activate angiogenic pathways that are not yet fully understood,patients must be made fully aware that they are participating in a non-standardized therapy whose outcomes,whether beneficial or harmful,cannot yet be predicted with certainty.This requires particularly careful medical communication,using simple yet scientifically accurate explanations delivered in appropriate language,along with a final verification of the patient’s actual understanding.
基金Ministry of Research,Innovation and Digitization,CCCDI-UEFISCDI,Grant/Award Number:PN-IV-P7-7.1-PED-2024-1578,within PNCDI Ⅳ.
文摘Pathological scarring,manifested in the form of hypertrophic scars(HTS)and keloid scars(KS),represents a major clinical challenge due to its aesthetic and functional implications for patients.Understanding the molecular mechanisms involved in these types of scars and developing effective treatments requires the use of controlled ex-perimental models,especially animals,to overcome the limitations of clinical studies.The aim of this sistematic review is to critically analyze the animal models used in the last five years(2020-2025)for the study of pathological scars,highlighting their advantages,limitations and applicability in the development of new therapeutic strat-egies.Murine,rabbit and porcine models,as well as alternative models,offer varied perspectives on the formation and treatment of HTS and KS,with an emphasis on histological and molecular correlations with human pathology.By synthesizing recent data,the paper highlights the essential role of preclinical research in optimizing an-tifibrotic treatments and in advancing the translation of data into the clinical sphere.Overall,animal models remain essential for bridging mechanistic insights with clinical translation,supporting the development of more effective and personalized anti-scar therapies.
基金Science and Technology Planning Project of Guangdong Province,2023B1212060048,Xiande Xie。
文摘Recovered samples of Jilin H5 chondrite experimentally shocked to 12-133 GPa were studied to explore the behavior of opaque minerals under shock loading using SEM-EDS,Raman spectroscopy,and TIMA.The following results were obtained.Firstly,at pressures lower than 53GPa,the opaque minerals still keep the unmelted state,while at 78 GPa and higher,FeNi metal and troilite form eutectic intergrowths occurring as disorderly fine veinlets filling the shock-induced fractures in silicate minerals.Secondly,single kamacite grains still maintain their contour at 12 GPa,but a part of brittle troilite grains was fragmented and squeezed into the shock-induced fractures within kamacite grains.At53 and 133 GPa,many more troilite fragments are poured in the kamacite interior to form disordered hybrid aggregates or to form squiggly strips,respectively.Similar phenomena are observed within single troilite grains,but the mineral squeezed into troilite grains is kamacite.Thirdly,chromite is a hard and refractory oxide mineral.When the shock pressure rises step by step from 12 to 133 GPa,the shock effect of chromite is only fragmentation.Its grain size decreases from tens of um at 53 GPa to a few um at 133 GPa.And,fourthly,native copper exhibits distinct redistribution behavior at high temperature.In Jilin samples shock-loaded to 12 GPa,copper initially located at troilite-kamacite interfaces partially transferred into small troilite grains containing fine FeNi particles.At 53 and 133 GPa,native copper preferentially transferred into larger troilite grains containing more particles of eutectic FeNi metal.
基金Supported by Undergraduate Higher Education Teaching Quality and Reform Projects of Guangdong Province(Yuejiao Gao Han[2024]No.9,Yuejiao Gao Han[2024]No.30)Guangdong Basic and Applied Basic Research Foundation(2023A1515110973)+1 种基金Guangdong Provincial Young Innovative Talents Project of General Colleges and Universities(2023KQNCX089)Quality Engineering and Teaching Reform Projects of Zhaoqing University(zlgc202239,zlgc202207,zlgc2024005,zlgc2024038).
文摘To meet the need for cultivating application-oriented talents in local universities,this study introduced a project-based learning approach into the reform of bioinformatics experimental teaching.The course was structured around a project titled"Influenza Virus Analysis",comprising four progressive modules:database utilization and information retrieval,sequence alignment and phylogenetic analysis,functional and structural prediction,and omics data analysis.These modules were integrated into a coherent research workflow that connected fragmented knowledge and technical skills.During implementation,flipped classroom and group collaboration methods were employed,alongside the establishment of a diversified assessment system emphasizing process evaluation.Teaching practice indicates that the reform effectively enhances students professional application skills,learning experience,and scientific literacy,facilitating a shift from"tool operation"to"problem-solving"capabilities.This study provides a reference model for the reform of bioinformatics experimental teaching in local universities.
基金supported by the National Natural Science Foundation of China(No.52388102)the Sichuan Science and Technology Program(No.2024NSFTD0011)the Fundamental Research Funds for the State Key Laboratory of Rail Transit Vehicle System of Southwest Jiaotong University(No.2023TPL-T11).
文摘The dynamic characteristics of the track system can directly affect its service performance and failure process.To explore the load characteristics and dynamic response of the track system under the dynamic loads from the rack vehicle in traction conditions,a systematic test of the track subsystem was carried out on a large-slope test line.In the test,the bending stress of the rack teeth,the wheel-rail forces,and the acceleration of crucial components in the track system were measured.Subsequently,a detailed analysis was conducted on the tested signals of the rack railway track system in the time domain and the time-frequency domains.The test results indicate that the traction force significantly affects the rack tooth bending stress and the wheel-rail forces.The vibrations of the track system under the traction conditions are mainly caused by the impacts generated from the gear-rack engagement,which are then transferred to the sleepers,the rails,and the ballast beds.Furthermore,both the maximum stress on the racks and the wheel-rail forces measured on the rails remain below their allowable values.This experimental study evaluates the load characteristics and reveals the vibration characteristics of the rack railway track system under the vehicle’s ultimate load,which is very important for the load-strengthening design of the key components such as racks and the vibration and noise reduction of the track system.
基金supported by the National Natural Science Foundation of China(Grant Nos.42407267 and 52374152)the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20220975).
文摘Time-delayed blasting is widely utilized in engineering to mitigate induced vibration hazards and enhance fragmentation.The underlying vibration reduction principle is the decrease of the charge weight per delay,while the potential for further vibration reduction remains debated,largely due to unclear underlying mechanisms.In light of the popularization of electronic detonators and the representativeness of double-hole configurationsfor multiple blastholes,it is essential to investigate the vibration characteristics induced by time-delayed double blastholes.Therefore,a series of doubleborehole experimental blasts was conducted in an underground roadway to clarify the variation in vibration from single-hole to dual-hole conditions.Based on the experimental data and inherent limitations,an exact full-fieldtheoretical model was further employed to systematically analyze the effects of delay time,charge length,and borehole inclination angle on vibrations induced by various doublehole configurations.The experimental data and theoretical analysis reveal that the general scaled distance effectively predicts vibrations in delayed blasting but does not reflectvibration reduction.Increasing delay time causes fluctuatingPPVs,which stabilize slightly above single-hole PPVs as delay times exceed a certain value.The delayed blasting primarily reduces near-fieldfrequencies.Longer charge lengths in double boreholes increase PPV levels and attenuation rates within a certain length,and the vibration behavior of combined long and short charge lengths is governed by the long blasthole.Larger blasthole inclination angles enhance vibration amplitude and reduce PPV attenuation rates.Optimizing inclination angles is more critical than adjusting delay times,and parallel boreholes offer the best vibration control.
基金supported by National Natural Science Foundation of China(82205237)Matching Project for the Youth Fund of the National Natural Science Foundation at Nanjing University of Chinese Medicine(XPT82205237)Jiangsu Provincial Department of Health Medical Science Research Project(Z2021065).
文摘Objective:To assess the effectiveness and safety of the Fuzheng Buxue Dietary Therapy(FBDT)for mitigating myelosuppression caused by chemotherapy containing platinum agents.Methods:In this non-randomized concurrent controlled trial,70 chemotherapy patients were evenly divided into two groups:the FBDT group and a standard care control group.The control group adhered to the standard oncological treatment protocol.Meanwhile,the FBDT group,in addition to the standard regimen,took an additional 300ml of the formula daily with lunch,beginning one week prior to chemotherapy and lasting for two weeks.The study conducted a comprehensive comparative analysis of peripheral blood counts,Traditional Chinese Medicine(TCM)symptom scores,Karnofsky Performance Status(KPS)scores,and the incidence of adverse reactions among patients from both groups.Outcomes:A total of 64 patients completed the study,with 32 in each group.FBDT group exhibited a significantly higher white blood cells recovery level one and three weeks after the chemotherapy compared to control group(3.23±0.68 vs 2.76±0.75(×10^(9)/L);3.92±1.07 vs 3.44±0.91(×10^(9)/L);P<0.05).Furthermore,three weeks after the start of chemotherapy,FBDT group had higher platelet recovery levels than the control group(164.25±54.38 vs 124.81±47.88(×10^(9)/L),P<0.05).Additionally,the TCM syndrome scores in FBDT group were lower(P<0.05),and the KPS scores were significantly higher in FBDT group(P<0.05).No serious adverse events were observed in two groups.Conclusion:FBDT is effective and safe in reducing myelosuppression caused by platinum chemotherapy.Future study should involve larger,multicenter trials to better understand dose-response and overall therapeutic value of FBDT.
基金This study was funded by the Natural Science Foundation of Guangdong Province (No. 001355).
文摘Objective: To study the effects of angiostatin (AS) gene mediated by liposome on human pancreatic cancer cell line SW1990. Methods: Angiostatin gene was cloned into the eu- karyotic expression vector pRC/CMV. The recombi- nant of pRC/CMV-AS was introduced into the pan- creatic cancer cell line, SW1990. The mechanism of anti-tumor was studied and tested. Results: The eukaryotic expression vector pRC/ CMV-AS was identified by the restriction digest. pRC/CMV-AS was stably integrated into the target cells and expressed by Western blot and drug-sensi- tivity tests, and inhibited the vascular endothelial cells proliferation in vitro. In addition, the effects of the angiostatin vector on reducing the volume of tumors implanted in nude mouse models were also noted. Conclusion: This study demonstrated that the recom- binant pRC/CMV-AS mediated by liposome may play a potential role in the treatment of pancreatic cancer in the future.
文摘Oxidative stress has been shown to play an important role in the pathogenesis of acute pancreatitis (AP). Antioxidants, alone or in combination with conventional therapy, should improve oxidative-stress-induced organ damage and therefore accelerate the rate of recovery. In recent years, substantial amounts of data about the efficiency of antioxidants against oxidative damage have been obtained from experiments with rodents. Some of these antioxidants have been found beneficial in the treatment of AP in humans; however, at present there is insufficient clinical data to support the benefits of antioxidants, alone or in combination with conven-tional therapy, in the management of AP in humans. Conflicting results obtained from experimental animals and humans may represent distinct pathophysiological mechanisms mediating tissue injury in different species. Further detailed studies should be done to clarify the exact mechanisms of tissue injury in human AP. Herein I tried to review the existing experimental and clinical studies on AP in order to determine the efficiency of antioxidants. The use of antioxidant enriched nutrition is a potential direction of clinical research in AP given the lack of clues about the efficiency and safety of antioxidant usage in patients with AP.
文摘The liver is an exceptional organ,not only because of its unique anatomical and physiological characteristics,but also because of its unlimited regenerative capacity.Unfolding of the molecular mechanisms that govern liver regeneration has allowed researchers to exploit them to augment liver regeneration.Dramatic progress in the field,however,was made by the introduction of the powerful tool of gene therapy.Transfer of genetic materials,such as hepatocyte growth factor,using both viral and non-viral vectors has proved to be successful in augmenting liver regeneration in various animal models.For future clinical studies,ongoing research aims at eliminating toxicity of viral vectors and increasing transduction efficiency of non-viral vectors,which are the main drawbacks of these systems.Another goal of current research is to develop gene therapy that targets specific liver cells using receptors that are unique to and highly expressed by different liver cell types.The outcome of such investigations will,undoubtedly,pave the way for future successful clinical trials.
文摘Objective:To investigate the effect of diminazene aceturale(DA) alone or in combination with either levamisole and/or Vitamin C in albino rats experimentally infected with Trypanosoma brucei brucei.Methods:Thirty adult male albino rats,randomly assigned into 6 groups(A—F) of 5rats each were used.They were either infected with 1×10~a trypanosomes intraperitoneally(groups A-E) or uninfected(group F).The different groups were treated respectively as follows:group A-with 3.5 mg/kg DA;group B-3.5 mg/kg DA and 7.5 mg/kg levamisole;group C-3.S mg/kg DA and 100 mg/kg vitamin C;and group D-3.S mg/kg DA and 7.S mg/kg levamisole and 100 mg/kg vitamin C.Croup E was left untreated.Parameters assessed include:rectal temperature,body weight changes,packed cell volume(PCV),Haemoglobin concentration(Hb),total leucocyte count(TLC) differential leucocyte count(DLC),parasitaemia,clinical signs and survivability.Results:Average pre-patent period of 5 days was recorded.Parasites in the blood were cleared in all treated groups(A-D) within 48 hours post treatment(PT).Untreated rats in group E died between25 and 32 days post infection(PI).Relapse was not recorded in all the treated groups(A-D).The initial reduction in PCV,Hb,TLC and increases in rectal temperature following infection were reversed by the treatments.The rats that received drug combinations(groups B,C and D)showed faster and higher recovery rates than the uninfected control and group A.Conclusions:Levamisole and/or Vitamin C combination with DA were more effective in the treatment of rats infected with Trypanosoma brucei brucei.
文摘This study was designed to establish an animal model of gastric mucosal precancerous lesions in Wistar rats and on this model, the mechanism to produce the precancerous lesions and their reverse therapy were studied. Ranitidine (R) 0.03% in the diet, N-methyl-N'-nitro-N-nitrosoguanidine(MNNG)50 μg/ml in drinking water, or both of them were administered to Wistar rats for 20 weeks. The iats were maintained without the drugs for additional 23 weeks. A control group of rats without any treatment of drugs were kept for 43 weeks Intestinal metaplasia (IM) was found in 86.5% of the rats in MNNG group, 22.5% in R groupand 100% in MNNG+R while only 7.5% in the control. The incidence of IM was significantly different between MNNG+R group and R group or MNNG group. The number of metaplastic glands was also the highest in the MNNG+R group. The therapeutic effects of retinoic acid (RA) and sodium butyrate (SB) on the iNduced precancerousous lesions of the glandular gastric mucosa were observed. It was found that the incidence of IM, moderate and severe dysplasia, and gastric cancer and the number of metaplastic glands in the pylorus and fundus were significantly lower in RA treated group (72.0%, 24.0%, 0%, 130.2±93.9 and 51.5±39.1) and SB treated gioup (60.0%,20.0%, 0%, 70.3±46.8, and 39.8±29.6) than in the RA untreated group (100%, 52.2%, 16.0%, 442.4±230.0 and 247.4±112.07) and the SB untreated group (88.0%, 48.0%. 16.0%, 241.4±113.9 and 146.4±66.3)(P<0.01 to 0.05). A mucosal flap with vascular pedicle from the gastric wall of the Wistar rats was transplanted to the duodenum, jejunum and colon respectively and the rats were killed in the 3td, 6th, 9th and 12th month after operation. IM was found in all the gastric grafts to the intestines with optical and electron microscopy. It is concluded on the basis of the findings that the concomitant administration of MNNG and R is a reliable method to induce IM of gastric mucosa in rats; RA and SB are efficient agents for the reverse thevapy of the precancerous lesions of gastric glandular mucosa in rats; and the formation of IM of gastric mucosa might be a pH-related process. The possible mechanism of the development of IM was discussed.
基金ThisprojectwassupportedbyagrantfromNationalNaturalSciencesFoundationofChina (No 30 170 94 5 )
文摘To explore a new method for the therapy of the avascular necrosis of the femoral head, the recombinant plasmid pCD-hVEGF 165 was mixed with collagen and was implanted in the necrotic femoral head The expression of vascular endothelial growth factor (VEGF) was detected by RNA dot hybridization and immunohistochemical method The repair of the femoral head was observed by histological method The results showed that the expression of VEGF was detectable in the femoral head treated with VEGF gene Angiogenesis in these femoral heads was more abundant than the control Bone repairing was augmented in the femoral head treated with VEGF gene The results suggest that angiogenesis in bone tissue could be augmented by gene transfection of VEGF and bone repairing would be accelerated accordingly
文摘The absence of effective therapies for castration-resistant prostate cancer(CRPC) establishes the need to develop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of "bystander effect". Consequently, scientists all over the world focus their main experimental research on the following four aspects: targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer.
文摘AIM： To investigate the individual and combined effects of allopurinol and hyperbaric oxygen （HBO） therapy on biochemical and histopathological changes, oxidative stress, and bacterial translocation （BT） in the experimental rat acute pancreatitis （AP）. METHODS： Eighty-five Sprague-Dawley rats were included in the study. Fifteen of the eighty-five rats were used as controls （sham, Group I ）. AP was induced via intraductal taurocholate infusion in the remaining seventy rats. Rats that survived to induction of acute necrotizing pancreatitis were randomized into four groups. Group H received saline, Group m allopurinol, Group IV allopurinol plus HBO and Group v HBO alone. Serum amylase levels, oxidative stress parameters, BT and histopathologic scores were determined. RESULTS： Serum amylase levels were lower in Groups Ⅲ, Ⅳ and v compared to Group H （974 ± 110, 384 ± 40, 851 ＋ 56, and 1664 Ⅳ 234 U/L, respectively, P 〈 0.05, for all）. Combining the two treatment optionsrevealed significantly lower median [25-75 percentiles] histopathological scores when compared to individual administrations （13 [12.5-15] in allopurinol group, 9.5 [7-11.75] in HBO group, and 6 [4.5-7.5] in combined group, P 〈 0.01）. Oxidative stress markers were significantly better in all treatment groups compared to the controls. Bacterial translocation into the pancreas and mesenteric lymph nodes was lower in Groups m, iV and v compared to Group H （54%, 23%, 50% vs 100% for translocation to pancreas, and 62%, 46%, 58% vs 100% for translocation to mesenteric lymph nodes, respectively, P 〈 0.05 for all）. CONCLUSION： The present study confirms the benefit of HBO and allopurinol treatment when administered separately in experimental rat AP. Combination of these treatment options appears to prevent progression of pancreatic injury parameters more effectively.
基金Project (No. 7002691) supported by the Guangdong Provincial Natural Science Foundation of China
文摘Background and objective:Gonadotropin-releasing hormone (GnRH) plays an important role in the regulation of ovarian function and ovarian cancer cell growth. In this study, we determined whether administration of the GnRH agonist (GnRHa), triporelin, prior to cisplatin treatment affects cisplatin and/or prevents cisplatin-induced ovarian damage. Methods:nu/nu mice were injected with ovarian cancer OVCAR-3 cells intraperitoneally. After two weeks, the mice were treated with saline (control), cisplatin, GnRHa, or cisplatin plus GnRHa for four weeks. At the end of the experimental protocol, blood, tumor, ovary, and uterine tissues were resected for hematoxylin and eosin (H&E) staining, immunohistochemical analyses of Ki67, nuclear factor-κB (NF-κB), and caspase-3, transmission electron microscopy of apoptosis, or enzyme-linked immunosorbent assay (ELISA) analyses of anti-Mullerian hormone (AMH). Results:Cisplatin treatment effectively inhibited tumor growth in mice treated with human ovarian cancer cells; however the treatment also induced considerable toxicity. Immunohistochemical analyses showed that Ki67 expression was reduced in cisplatin-treated mice compared to control (P<0.05), but there was no statistically significant differences between cisplatin-treated mice and cisplatin plus GnRHa-treated mice (P>0.05), while expressions of NF-κB and caspase-3 were reduced and induced, respectively, in cisplatin-treated mice and cisplatin plus GnRHa-treated mice. Apoptosis occurred in the GnRHa, cisplatin, and cisplatin plus GnRHa-treated mice, but not in control mice. Ovaries exposed to GnRHa in both GnRHa mice and cisplatin-treated mice (combination group) had significantly more primordial and growth follicles and serum levels of AMH than those in the control mice and cisplatin-treated mice (P<0.05). Conclusions:Administration of GnRHa to mice significantly decreased the extent of ovarian damage induced by cisplatin, but did not affect the anti-tumor activity of cisplatin.
基金United Arab Emirates University,Grant/Award Number:12R104 and 12R121。
文摘Cardiac injury initiates repair mechanisms and results in cardiac remodeling and fi-brosis,which appears to be a leading cause of cardiovascular diseases.Cardiac fi-brosis is characterized by the accumulation of extracellular matrix proteins,mainly collagen in the cardiac interstitium.Many experimental studies have demonstrated that fibrotic injury in the heart is reversible;therefore,it is vital to understand differ-ent molecular mechanisms that are involved in the initiation,progression,and resolu-tion of cardiac fibrosis to enable the development of antifibrotic agents.Of the many experimental models,one of the recent models that has gained renewed interest is isoproterenol(ISP)-induced cardiac fibrosis.ISP is a synthetic catecholamine,sympa-thomimetic,and nonselectiveβ-adrenergic receptor agonist.The overstimulated and sustained activation ofβ-adrenergic receptors has been reported to induce biochemi-cal and physiological alterations and ultimately result in cardiac remodeling.ISP has been used for decades to induce acute myocardial infarction.However,the use of low doses and chronic administration of ISP have been shown to induce cardiac fibrosis;this practice has increased in recent years.Intraperitoneal or subcutaneous ISP has been widely used in preclinical studies to induce cardiac remodeling manifested by fibrosis and hypertrophy.The induced oxidative stress with subsequent perturbations in cellular signaling cascades through triggering the release of free radicals is consid-ered the initiating mechanism of myocardial fibrosis.ISP is consistently used to induce fibrosis in laboratory animals and in cardiomyocytes isolated from animals.In recent years,numerous phytochemicals and synthetic molecules have been evaluated in ISP-induced cardiac fibrosis.The present review exclusively provides a comprehensive summary of the pathological biochemical,histological,and molecular mechanisms of ISP in inducing cardiac fibrosis and hypertrophy.It also summarizes the application of this experimental model in the therapeutic evaluation of natural as well as syn-thetic compounds to demonstrate their potential in mitigating myocardial fibrosis and hypertrophy.
文摘Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.
文摘Objectives： To assess the genotoxic effect of a new antitumor ozone-photodynamic therapy using the improvedmodification of the COMET assay. Methods： Xenograft cancer models on 58 rats were used. The sarcoma RA was transplantedsubcutaneously, and after increasing of tumor volume from 0.5 to 4.2 cm3, rats were divided into the four groups： ＂Intact＂--healthy,＂Control＂--with xenografted tumors and no treatment, ＂PDT＂--the rats treated with the photodynamic therapy, ＂PDT ＋ozone＂--the rats were treated with both photodynamic therapy and injections of ozonated saline solution. The toxicity of treatmentwas assessed by DNA damage in leukocytes using the new modification of the COMET assay. The analysis of the ＂COMETs＂ wasperformed following the percentage of DNA in the tail of the ＂COMET＂ （% TDNA）. Results： A combination of PDT and ozonemakes the strongest negative impact on tumor growth. The tumor growth inhibition is associated with low genotoxic exposure ofozone-photodynamic therapy on whole blood leukocytes of cancer rats. Conclusions： A new modification of the COMET assay canprovide the assessment of the genotoxic effect of the antitumor therapy in experimental neoplasia.
文摘To study the therapeutic effects of herpes simplex virus thymidine kinase gene transferred by the EBV based expression vector on experimental hepatocellular carcinoma, pDR2 TK gene was delivered into human hepatocellular carcinoma cell line SMMC 7721 by using liposome mediated transfection technique,and then gene expression was detected by RT PCR, and the killing effects were examined through MTT method. In the nude mice hepatoma model,the antitumor effects of pDR2 TK /GCV system was evaluated in terms of tumor growth. MTT results showed that the pDR2 TK /GCV had cytotoxic effect and about 70 % SMMC 7721 cells were killed when GCV was at 1000 μmol/L. In vivo experiment showed that the tumor size in nude mice with transferred pDR2 TK gene was significantly smaller than that in control group . On the 10th day the tumor in 3 mice (60 %) disappeared completely after GCV treatment. It is concluded that the pDR2 TK/GCV system has marked killing effects on the experimental hepatocellular carcinoma.
