1.Biological principles for "homotherapy for heteropathy"
Wei-jia KONG ; Yu-huan LI ; Jian-dong JIANG
Acta Pharmaceutica Sinica 2024;59(2):269-278
Non-infectious chronic diseases in human including diabetes, non-alcoholic fatty liver disease (NAFLD), atherosclerosis (AS), neurodegenerative diseases, osteoporosis, as well as malignant tumors may have some common pathogenic mechanisms such as non-resolved inflammation (NRI), gut microbiota dysfunction, endoplasmic reticulum stress, mitochondria dysfunction, and abnormality of the mammalian target of rapamycin (mTOR) pathway. These pathogenic mechanisms could be the basis for "homotherapy for heteropathy" in clinic. Some commonly used clinical drugs, such as metformin, berberine, aspirin, statins, and rapamycin may execute therapeutic effect on their targeted diseases,and also have the effect of "homotherapy for heteropathy". The mechanisms of the above drugs may include anti-inflammation, modulation of gut microbiota, suppression of endoplasmic reticulum stress, improvement of mitochondria function, and inhibition of mTOR. For virus infectious diseases, as some viruses need certain commonly used replicases, the inhibitors of the replicases become examples of "homotherapy for heteropathy" for antiviral therapy in clinic (for example tenofovir for both AIDS and HBV infection). Especially, in case of outbreak of new emerging viruses, these viral enzyme inhibitors such as azvudine and sofibuvir, could be rapidly used in controlling viral epidemic or pandemic, based on the principle of "homotherapy for heteropathy". In this review article, we show the research progress of the biological basis for "homotherapy for heteropathy" and the possible mechanisms of some well-known drugs, in order to provide insights and new references for innovative drug R&D.
2.Neurotrophin-3 promotes the recovery of neurological function after cerebral ischemia-reperfusion injury in rats
Yan CONG ; Yanfei WANG ; Wenchao DONG ; Jian YU
Chinese Journal of Neuroanatomy 2024;40(1):78-84
Objective:To explore the role and mechanism of neurotrophin-3(NT-3)in promoting neurological func-tion recovery after cerebral ischemia-reperfusion injury in rats.Methods:Twenty-four SD rats were randomly divided into sham operation group(Sham),middle cerebral artery occlusion/reperfusion(MCAO/R)group,and MCAO/R+NT-3 group.The neurological function scores of rats in each group were evaluated using the modified Garcia score.Western Blot was used to detect the expression of NT-3 and LC3B in brain tissues of rats.Culture dishes with the same density of neurons were randomly divided into normal group(Normal),oxygen-glucose deprivation(OGD)group,OGD+NT-3 group,OGD+NT-3+PF-06273340(TrkC inhibitor)group,OGD+NT-3+ZSTK474(PI3K inhibitor)group,and OGD+NT-3+CCT128930(AKT inhibitor)group.Western Blot was used to detect the expression of TrkC,the phosphorylation of PI3K/AKT,and LC3B in neurons.The morphological changes of neurons and the phenomenon of neuronal autophagy were observed using autophagy-specific fluorescent staining.Results:The animal experiment found that the expression of NT-3 increased in the brain tissue with ischemia-reperfusion injury(P<0.05),and after the treatment with exogenous NT-3,the modified Garcia score increased(P<0.05),and the level of autophagy weakened(P<0.05).The cell experiment found that NT-3 can inhibit neuronal autophagy under ischemic hypoxia and maintain the neuronal morphology to the maximum extent.After using PF-06273340,the expression of p-PI3K and p-AKT de-creased(P<0.05).After using ZSTK474 and CCT128930,the autophagy-inhibiting effect of NT-3 weakened(P<0.05).Conclusion:NT-3 inhibits autophagy via the PI3K/AKT signaling pathway to maintain neuronal survival,thereby promoting the recovery of neurological function after cerebral ischemia-reperfusion injury in rats.
3.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
4.Bioequivalence study of ezetimibe tablets in Chinese healthy subjects
Pei-Yue ZHAO ; Tian-Cai ZHANG ; Yu-Ning ZHANG ; Ya-Fei LI ; Shou-Ren ZHAO ; Jian-Chang HE ; Li-Chun DONG ; Min SUN ; Yan-Jun HU ; Jing LAN ; Wen-Zhong LIANG
The Chinese Journal of Clinical Pharmacology 2024;40(16):2378-2382
Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90%CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90%CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.
5.Role of Hedgehog signaling pathway in muscle bone symbiosis in osteo-sarcopenia
Yan-Dong LIU ; Qiang DENG ; Zhong-Feng LI ; Ran-Dong PENG ; Yu-Rong WANG ; Jia-Ming LI ; Ping-Yi MA ; Jian-Qiang DU
The Chinese Journal of Clinical Pharmacology 2024;40(16):2433-2437
This article elaborates on the complex cross-talk and close relationship between muscles and bones involved in this disease,as well as its pathogenesis.It also summarizes that the difficulty of its treatment lies in the need to simultaneously consider both muscles and bones.And elaborated on the key role of the Hedgehog signaling pathway in embryonic development,tissue morphology establishment,and human tissue regeneration and repair.Investigated the remodeling effect of the Hedgehog signaling pathway on skeletal muscle from three aspects:Proliferation and differentiation of muscle stem cells,precursor cell and muscle fiber generation,inhibition of inflammation,and regulation of immunity;this article elucidates the role of the Hedgehog signaling pathway in bone reconstruction from two aspects.
6.Species-level Microbiota of Biting Midges and Ticks from Poyang Lake
Jian GONG ; Fei Fei WANG ; Qing Yang LIU ; Ji PU ; Zhi Ling DONG ; Hui Si ZHANG ; Zhou Zhen HUANG ; Yuan Yu HUANG ; Ben Ya LI ; Xin Cai YANG ; Meihui Yuan TAO ; Jun Li ZHAO ; Dong JIN ; Yun Li LIU ; Jing YANG ; Shan LU
Biomedical and Environmental Sciences 2024;37(3):266-277,中插1-中插3
Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.
7.Salidroside Ameliorates Lung Injury Induced by PM2.5 by Regulating SIRT1-PGC-1α in Mice
Hong Xiao LI ; Mei Yu LIU ; Hui SHAN ; Feng Jin TAN ; Jian ZHOU ; Jin Yuan SONG ; Qi Si LI ; Chen LIU ; Qun Dong XU ; Li YU ; Wei Wan LI
Biomedical and Environmental Sciences 2024;37(4):367-376
Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.
8.Associations of onset age, diabetes duration and glycated hemoglobin level with ischemic stroke risk in type 2 diabetes patients: a prospective cohort study
Xikang FAN ; Mengyao LI ; Yu QIN ; Chong SHEN ; Yan LU ; Zhongming SUN ; Jie YANG ; Ran TAO ; Jinyi ZHOU ; Dong HANG ; Jian SU
Chinese Journal of Epidemiology 2024;45(4):498-505
Objective:To investigate the associations of onset age, diabetes duration, and glycated hemoglobin (HbA1c) levels with ischemic stroke risk in type 2 diabetes patients.Methods:The participants were from Comprehensive Research on the Prevention and Control of the Diabetes in Jiangsu Province. The study used data from baseline survey from December 2013 to January 2014 and follow-up until December 31, 2021. After excluding the participants who had been diagnosed with stroke at baseline survey and those with incomplete information on onset age, diabetes duration, and HbA1c level, a total of 17 576 type 2 diabetes patients were included. Cox proportional hazard model was used to calculate the hazard ratio ( HR) and 95% CI of onset age, diabetes duration, and HbA1c level for ischemic stroke. Results:During the median follow-up time of 8.02 years, 2 622 ischemic stroke cases were registered. Multivariate Cox proportional risk regression model showed that a 5-year increase in type 2 diabetes onset age was significantly associated with a 5% decreased risk for ischemic stroke ( HR=0.95, 95% CI: 0.92-0.99). A 5-year increase in diabetes duration was associated with a 5% increased risk for ischemic stroke ( HR=1.05, 95% CI: 1.02-1.10). Higher HbA1c (per 1 standard deviation increase: HR=1.17, 95% CI: 1.13-1.21) was associated with an increased risk for ischemic stroke. Conclusion:The earlier onset age of diabetes, longer diabetes duration, and high levels of HbA1c are associated with an increased risk for ischemic stroke in type 2 diabetes patients.
9.Content determination of seventeen amino acids in Gualoupi Injection and its intermediates and research on their change laws
Xiang TAO ; Jing-Xian ZHANG ; Qing HU ; Jian SUN ; Ying DONG ; Jin-Guo DING ; Hong YU ; Ying-Ying SHEN ; Xiu-Hong MAO ; Shen JI
Chinese Traditional Patent Medicine 2024;46(3):709-717
AIM To determine the contents of aspartic acid,glutamic acid,serine,glycine,threonine,citrulline,arginine,alanine,γ-amino-butyric acid,tyrosine,valine,phenlalanine,isoleucine,ornithine,leucine,lysine and proline in Gualoupi Injection and its intermediates,and to analyze their change laws.METHODS The OPA-FMOC online derivatization analysis was performed on a 45℃ thermostatic Waters XBridge C18 column(4.6 mm×100 mm,3.5 μm),with the mobile phase comprising of phosphate buffer solution-[methanol-acetonitrile-water(45 : 45 : 10)]flowing at 1 mL/min in a gradient elution manner,and the detection wavelengths were set at 262,338 nm.Principal component analysis and heatmap analysis were adopted in chemical pattern recognition for the corresponding intermediates in ten processes of six batches of samples.RESULTS Seventeen amino acids showed good linear relationships within their own ranges(R2>0.998 0),whose average recoveries were 83.4%-119.5%with the RSDs of 0.91%-7.94%.Different batches of samples in the same process were clustered,and the corresponding intermediates in different processed were clustered into three groups.Alcohol precipitation and cation exchange column demonstrated the biggest influences on amino acid composition.CONCLUSION This experiment can provide important references for the critical factors on quality control of Gualoupi Injection,thus ensure the stability and uniformity of final product.
10.Prevalence of non-alcoholic fatty liver disease and associated factors in overweight and obese children in Hohhot
YU Qiong, LI Jianying, CAO Puli, LIU Dong, ZHANG Jian, LI Ruifeng
Chinese Journal of School Health 2024;45(5):742-745
Objective:
To explore prevalence and associated factors of nonalcoholic fatty liver disease (NAFLD) in overweight and obese children in Hohhot City, so as to provide the oretical basis for developing health education plans and implementing prevention and treatment of NAFLD in children.
Methods:
A total of 156 overweight and obese children was enrolled from 4 primary schools in Hohhot City using cluster sampling method during 28th Aug. 2022 to 5th Mar. 2023. Height and weight were measured and body mass index was calculated, and fasting blood was taken in the early morning for fasting blood glucose, alanine aminotransferase, aspartate aminotransferase. Single factor analysis was conducted using ttest, χ2 test and Fishers exact probability method, while multivariate analysis was conducted using Logistic regression analysis and subject characteristic curves.
Results:
The differences in age, waist circumference, hip circumference, fasting glucose, alanine aminotransferase, aspartate aminotransferase, gamma glutamyltransferase, uric acid, and triglyceride were statistically significant between the nonNAFLD and the NAFLD group (U/t=1 070.0-2 164.0, P<0.05). Significant differences were observed in aspartate aminotransferase (AST) and uric acid levels (AST OR=1.16, 95%CI=1.04-1.28; uric OR=1.01, 95%CI=1.00-1.01, P<0.05). The area under a receiver operating characteristic were 0.737 for aspartate aminotransferase and 0.665 for uric acid, respectively.
Conclusions
The prevalence of NAFLD is high in overweight/obese children in Hohhot, and both elevated aspartate aminotransferase and hyperuricemia could increase the risk of NAFLD in overweight/obese children. Special attention should be paid to the NAFLD in overweight and obese children. It is recommended to reduce both BMI and uric level in the prevention and treatment of NAFLD to achieve better treatment outcomes.


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