Interaction of major facilitator superfamily domain containing 2A with the blood-brain barrier.

The functional and structural integrity of the blood-brain barrier is crucial in maintaining homeostasis in the brain microenvironment; however, the molecular mechanisms underlying the formation and function of the blood-brain barrier remain poorly understood. The major facilitator superfamily domain containing 2A has been identified as a key regulator of blood-brain barrier function. It plays a critical role in promoting and maintaining the formation and functional stability of the blood-brain barrier, in addition to the transport of lipids, such as docosahexaenoic acid, across the blood-brain barrier. Furthermore, an increasing number of studies have suggested that major facilitator superfamily domain containing 2A is involved in the molecular mechanisms of blood-brain barrier dysfunction in a variety of neurological diseases; however, little is known regarding the mechanisms by which major facilitator superfamily domain containing 2A affects the blood-brain barrier. This paper provides a comprehensive and systematic review of the close relationship between major facilitator superfamily domain containing 2A proteins and the blood-brain barrier, including their basic structures and functions, cross-linking between major facilitator superfamily domain containing 2A and the blood-brain barrier, and the in-depth studies on lipid transport and the regulation of blood-brain barrier permeability. This comprehensive systematic review contributes to an in-depth understanding of the important role of major facilitator superfamily domain containing 2A proteins in maintaining the structure and function of the blood-brain barrier and the research progress to date. This will not only help to elucidate the pathogenesis of neurological diseases, improve the accuracy of laboratory diagnosis, and optimize clinical treatment strategies, but it may also play an important role in prognostic monitoring. In addition, the effects of major facilitator superfamily domain containing 2A on blood-brain barrier leakage in various diseases and the research progress on cross-blood-brain barrier drug delivery are summarized. This review may contribute to the development of new approaches for the treatment of neurological diseases.

Border-associated macrophages: From physiology to therapeutic targets in Alzheimer's disease.

Border-associated macrophages (BAMs) constitute a highly heterogeneous group of central nervous system-resident macrophages at the brain boundaries. Despite their significance, BAMs have mainly been overlooked compared to microglia, resulting in a limited understanding of their functions. However, recent advancements in single-cell immunophenotyping and transcriptomic analyses of BAMs have revealed a previously unrecognized complexity in these cells, in addition to their critical roles under non-pathological conditions and diseases like Alzheimer's disease (AD), Parkinson's disease, glioma, and ischemic stroke. In this review, we discuss the origins, self-renewal capabilities, and extensive heterogeneity of BAMs, and clarify their important physiological functions such as immune monitoring, waste removal and vascular permeability regulation. We also summarize experimental evidence linking BAMs to the progression of AD. Finally, we review therapeutic strategies targeting brain innate immune cells mainly focusing on strategies aimed at modulating BAMs to treat AD and evaluate their potential in clinical applications.

Da-Jian-Zhong decoction alleviates diarrhea-predominant irritable bowel syndrome via modulation of gut microbiota and Th17/Treg balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive. AIM OF THE STUDY: We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms. MATERIALS AND METHODS: An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses. RESULTS: We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon. CONCLUSIONS: These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.

A Mechanism for the Treatment of Cardiovascular and Renal Disease: TRPV1 and TRPA1.

ABSTRACT: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. CVD and kidney disease are closely related, with kidney injury increasing CVD mortality. The pathogenesis of cardiovascular and renal diseases involves complex and diverse interactions between multiple extracellular and intracellular signaling molecules, among which transient receptor potential vanilloid 1 (TRPV1)/transient receptor potential ankyrin 1 (TRPA1) channels have received increasing attention. TRPV1 belongs to the vanilloid receptor subtype family of transient receptor potential ion channels, and TRPA1 belongs to the transient receptor potential channel superfamily. TRPV1/TRPA1 are jointly involved in the management of cardiovascular and renal diseases and play important roles in regulating vascular tension, promoting angiogenesis, antifibrosis, anti-inflammation, and antioxidation. The mechanism of TRPV1/TRPA1 is mainly related to regulation of intracellular calcium influx and release of nitric oxide and calcitonin gene-related peptide. Therefore, this study takes the TRPV1/TRPA1 channel as the research object, analyzes and summarizes the process and mechanism of TRPV1/TRPA1 affecting cardiovascular and renal diseases, and lays a foundation for the treatment of cardiorenal diseases.

Pharmacodynamics and mechanism of Erigeron breviscapus granules in the treatment of ischemic stroke in mice by regulating sphingolipid metabolism based on metabolomics.

AIM: Erigeron breviscapus (Vant.) Hand.-Mazz. (EB) granules is the extract preparation of EB, with clear curative effect and unclear mechanism. This study intends to systematically explore the specific mechanism of EB granules in the treatment of IS from the metabolic perspective. METHODS: The model of transient middle cerebral artery occlusion (tMCAO) in mice was established by the suture-occluded method. The therapeutic effect of EB granules on tMCAO mice was evaluated by behavioral evaluation, brain water content determination, 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and levels of lactate dehydrogenase (LDH) and neuron specific enolase (NSE) in serum. In order to screen differential metabolites, non-targeted metabolomics technology was used to detect the metabolites in serum before and after administration. Univariate statistics, multivariate statistics and bioinformatics were used to analyze the changes of metabolites in serum of tMCAO mice. The possible related mechanism of EB granules in treating IS was screened by pathway enrichment analysis, and the preliminary verification was carried out at animal level by enzyme linked immunosorbent assay (ELISA) and western blot (WB). RESULTS: EB granules could significantly improve behavior of tMCAO mice, reduce brain water content and cerebral infarction volume, improve morphology of brain tissue, reduce the levels of LDH and NSE in serum. A total of 232 differential metabolites were screened, which were mainly enriched in many biological processes such as sphingolipid metabolism. The differential metabolite S1P and its receptors S1PR1 and S1PR2 in sphingolipid metabolism were verified. The results showed that the level of S1P in brain tissue increased and the protein expression of S1PR1 decreased significantly after modeling, and reversed after administration, but there was no significant difference in the protein expression of S1PR2. CONCLUSION: The therapeutic effects of EB granules may be related to affecting sphingolipid metabolism through regulating S1P/S1PR1.

Natural products derived from herbs as promising source for diarrhea predominant-irritable bowel syndrome via gut microbiota-serotonin pathway.

OBJECTIVE: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal disorders, with diarrhea predominant IBS (IBS-D) as the most common subtype. Increasing evidence reported that the gut microbiota-mediated serotonin pathway plays a crucial role in the pathogenesis of IBS-D. In this study, potential herbal medicine, plant extracts and its monomers that can be employed as the candidate molecules for IBS-D through gut microbiota-mediated serotonin pathway were reviewed. KEY FINDINGS: The bacteria indigenous to gut microbiota regulates serotonin pathway, mainly increasing tryptophan hydroxylase (TPH) and decreasing serotonin reuptake transporter (SERT), by activating cyclooxygenase/prostaglandin E2 (COX/PGE2) signaling. It further accelerated gastrointestinal motility and visceral hyperalgesia. Herbal medicine prescription including Tongxie yaofang and Shugan decoction, as well as some monomers of flavonoid and polyphenol compounds can be regarded as the potential agents for IBS-D. The predominate mechanisms were related to regulating serotonin pathway by driving on the specific bacterial abundance (such as Firmicutes and Bacteroidetes). However, there are few reports on which specific bacteria species play a regulatory role in serotonin pathway, and most of these effective agents were only evidenced by preclinical studies. We hope this review will provide some useful directions for the treatment strategy of IBS-D.

Correlating facial skin parameters with age and gender in population of Shaanxi Province, China.

OBJECTIVE: This study was designed to comprehensively evaluate the changes in facial skin biophysical parameters with age, as well the influence of gender differences in populations of Shaanxi Province, China. METHODS: Fourteen skin parameters, including stratum corneum hydration (SCH), transdermal water loss (TEWL), erythema, melanin, R0, R2, R5, R7, F4, gloss, skin surface pH, skin erythema index (a*), wrinkle length, and sebum, were measured by noninvasive instruments in 481 volunteers from Shaanxi Province. Spearman correlation analysis was performed to analyze the relationship between skin parameters and age. Additionally, skin parameters were analyzed for different age groups and different genders. RESULTS: The results of the study showed a linear decrease in skin surface pH and sebum content with age, and the skin elasticity parameters R0, R2, R5, and R7 decreased significantly at the age of 54-65 years. Wrinkle length showed a linear and increase with age. R5 showed a weak negative correlation with age, R2, R7, and sebum content showed a moderate negative correlation, while wrinkle length showed a strong positive correlation. Considering the effect of gender on skin parameters, the results showed that SCH and gloss were lower in men than in women, while TEWL, erythema, melanin, wrinkle length, and sebum were higher than in women. However, there was no difference in skin elasticity between them. CONCLUSION: The facial skin parameters, especially for the wrinkle length, exhibited the strong correlation relationship with ages in Shaanxi Province. Meanwhile, most skin parameters show significant differences with gender, which can provide a reference for future research and development in the field of cosmetics.

Saponin of Aralia taibaiensis promotes angiogenesis through VEGF/VEGFR2 signaling pathway in cerebral ischemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Aralia taibaiensis is known for its ability to promote blood circulation and dispel blood stasis, activate meridians and remove arthralgia. The saponins of Aralia taibaiensis (sAT) are the main active components that are often used to treat cardiovascular and cerebrovascular diseases. However, it has not been reported whether sAT can improve ischemic stroke (IS) by promoting angiogenesis. AIM OF THE STUDY: In this study, we investigated the potential of sAT to promote post-ischemic angiogenesis in mice and determined the underlying mechanism through in vitro experiments. METHODS: To establish the middle cerebral artery occlusion (MCAO) mice model in vivo. First of all, we examined the neurological function, brain infarct volume, and degree of brain swelling in MCAO mice. We also observed pathological changes in brain tissue, ultrastructural changes in blood vessels and neurons, and the degree of vascular neovascularization. Additionally, we established the oxygen-glucose deprivation/reoxygenation (OGD/R) -human umbilical vein endothelial cells (HUVECs) model in vitro to detect the survival, proliferation, migration and tube formation of OGD/R HUVECs. Finally, we verified the regulatory mechanism of Src and PLCγ1 siRNA on sAT promoting angiogenesis by cell transfection technique. RESULTS: In the cerebral ischemia-reperfusion mice, sAT distinctly improved the cerebral infarct volume, brain swelling degree, neurological dysfunction, and brain histopathological morphology due to cerebral ischemia/reperfusion injury. It also increased the double positive expression of BrdU and CD31 in brain tissue, promoted the release of VEGF and NO and decreased the release of NSE and LDH. In the OGD/R HUVECs, sAT significantly improved cell survival, proliferation, migration and tube formation, promoted the release of VEGF and NO, and increased the expression of VEGF, VEGFR2, PLCγ1, ERK1/2, Src and eNOS. Surprisingly, the effect of sAT on angiogenesis was inhibited by Src siRNA and PLCγ1 siRNA in OGD/R HUVECs. CONCLUSION: The results proved that sAT promotes angiogenesis in cerebral ischemia-reperfusion mice and its mechanism is to regulate VEGF/VEGFR2 and then regulate Src/eNOS and PLCγ1/ERK1/2.

A systematic review and meta-analysis of the seroconversion rates and adverse effects of COVID-19 mRNA vaccine and COVID-19 viral vector vaccine in kidney transplant recipient patients.

Patients received kidney transplantation (KTR) have a low seroconversion rate after vaccination. Our objective was to compare the seroconversion rates and adverse effects of additional different vaccinations in KTR patients in existing studies. Databases such as PubMed, Cochrane Library, Web of Science, Embase, ClinicalTrials.gov and others. Three high-quality RCT were included and showed no statistical difference in seroconversion rates between the two vaccines (RR = 0.93[0.76,1.13]). There was no statistical difference in seroconversion rates between the sexes, for men (RR = 0.93[0.69,1.25]) and women (RR = 0.91[0.62,1.33]). Among the adverse effects there was no statistically significant difference in fever (RR = 1.06[0.44,2.57]), while for injection site pain there was a statistically significant difference (RR = 1.14[1.18,1.84]). There was no significant difference in seroconversion rates in patients with KTR who received the two additional vaccines. Patients injected with the viral vector vaccine were less painful than those injected with the mRNA vaccine.

Evaluation of mulberry leaves' hypoglycemic properties and hypoglycemic mechanisms.

The effectiveness of herbal medicine in treating diabetes has grown in recent years, but the precise mechanism by which it does so is still unclear to both medical professionals and diabetics. In traditional Chinese medicine, mulberry leaf is used to treat inflammation, colds, and antiviral illnesses. Mulberry leaves are one of the herbs with many medicinal applications, and as mulberry leaf study grows, there is mounting evidence that these leaves also have potent anti-diabetic properties. The direct role of mulberry leaf as a natural remedy in the treatment of diabetes has been proven in several studies and clinical trials. However, because mulberry leaf is a more potent remedy for diabetes, a deeper understanding of how it works is required. The bioactive compounds flavonoids, alkaloids, polysaccharides, polyphenols, volatile oils, sterols, amino acids, and a variety of inorganic trace elements and vitamins, among others, have been found to be abundant in mulberry leaves. Among these compounds, flavonoids, alkaloids, polysaccharides, and polyphenols have a stronger link to diabetes. Of course, trace minerals and vitamins also contribute to blood sugar regulation. Inhibiting alpha glucosidase activity in the intestine, regulating lipid metabolism in the body, protecting pancreatic -cells, lowering insulin resistance, accelerating glucose uptake by target tissues, and improving oxidative stress levels in the body are some of the main therapeutic properties mentioned above. These mechanisms can effectively regulate blood glucose levels. The therapeutic effects of the bioactive compounds found in mulberry leaves on diabetes mellitus and their associated molecular mechanisms are the main topics of this paper's overview of the state of the art in mulberry leaf research for the treatment of diabetes mellitus.

Peptidoglycan recognition protein MsPGRP in largemouth bass (Micropterus salmoides) mediates immune functions with broad nonself recognition ability.

Peptidoglycan (PGN) recognition proteins (PGRPs) are important immune factors in innate immunity that function in recognising pathogens and activating the immune system. These ubiquitous proteins are conserved in invertebrates and vertebrates. In this study, a PGRP gene (MsPGRP) from largemouth bass (Micropterus salmoides) was identified and characterised, and its transcription distribution was explored. Recombinant protein (rMsPGRP) exhibited dose-dependent binding to PGN and glucan (GLU), but weak binding to lipopolysaccharide (LPS). MsPGRP exhibited agglutinating activity against several Gram-negative bacteria, Gram-positive bacteria and fungi, and it promoted phagocytosis activity of leukocytes against Micrococcus luteus and Aeromonas hydrophila. The protein also possessed amidase activity in the presence of Zn2+, degraded PGN, and disrupted the M. luteus cell wall. The results suggest that MsPGRP plays an important role in pathogen recognition, and acts as a opsonin during immune system responses and elimination of invading pathogens.

The efficacy and safety of Chinese herbal medicine Guizhi Fuling capsule combined with low dose mifepristone in the treatment of uterine fibroids: a systematic review and meta-analysis of 28 randomized controlled trials.

OBJECTIVE: Guizhi Fuling Capsule (GZFL), a classic traditional Chinese medicine prescription, is often recommended for the treatment of uterine fibroids (UFs). However, the efficacy and safety of GZFL in combination with low-dose mifepristone (MFP) remains controversial. MATERIALS AND METHODS: We searched eight literature databases and two clinical trial registries for randomized controlled trials (RCTs) of the efficacy and safety of GZFL combined with low-dose MFP in the treatment of UFs from database inception to April 24, 2022. Data analysis was performed using the Meta package in RStudio and RevMan 5.4. GRADE pro3.6.1 software was used for the assessment of evidence quality. RESULTS: Twenty-eight RCTs were included in this study, including a total of 2813 patients. The meta-analysis showed that compared with low-dose MFP alone, GZFL combined with low-dose MFP significantly reduced follicle stimulating hormone (p < 0.001), estradiol (p < 0.001), progesterone (p < 0.001), luteinizing hormone (p < 0.001), uterine fibroids volume (p < 0.001), uterine volume (p < 0.001), menstrual flow (p < 0.001) and increased clinical efficiency rate (p < 0.001). Meanwhile, GZFL combined with low-dose MFP did not significantly increase the incidence of adverse drug reactions compared with low-dose MFP alone (p = 0.16). The quality of the evidence for the outcomes ranged from "very low" to "moderate." CONCLUSION: This study suggests that GZFL combined with low-dose MFP is more effective and safe in the treatment of UFs, and it is a potential treatment for UFs. However, due to the poor quality of the included RCTs formulations, we recommend a rigorous, high-quality, large-sample trial to confirm our findings.

Construction and imaging of a neurovascular unit model.

In 2001, the concept of the neurovascular unit was introduced at the Stroke Progress Review Group meeting. The neurovascular unit is an important element of the health and disease status of blood vessels and nerves in the central nervous system. Since then, the neurovascular unit has attracted increasing interest from research teams, who have contributed greatly to the prevention, treatment, and prognosis of stroke and neurodegenerative diseases. However, additional research is needed to establish an efficient, low-cost, and low-energy in vitro model of the neurovascular unit, as well as enable noninvasive observation of neurovascular units in vivo and in vitro. In this review, we first summarize the composition of neurovascular units, then investigate the efficacy of different types of stem cells and cell culture methods in the construction of neurovascular unit models, and finally assess the progress of imaging methods used to observe neurovascular units in recent years and their positive role in the monitoring and investigation of the mechanisms of a variety of central nervous system diseases.

Clinical Efficacy Evaluation and Potential Mechanism of Zhishe Tongluo Capsule in the Treatment of Cerebral Infarction by Meta-Analysis Associated with Network Pharmacology.

OBJECTIVE: By integrating meta-analysis and network pharmacology strategy, the clinical efficacy of Zhishe Tongluo capsule in the treatment of cerebral infarction was evaluated, and the intervention mechanism was preliminary explored. METHODS: Through meta-analysis, the Chinese and English literature of the randomized controlled trial (RCT) of Zhishe Tongluo capsule in the treatment of cerebral infarction was comprehensively searched. Based on the standard of Na Pai, the quantitative literature was determined and the Review Manager data were statistically analyzed. RESULTS: A total of 10 RCTs literatures were included. These literatures included a total of 1278 subjects, of which 670 were in the treatment group and 608 were in the control group. In terms of indicators of efficiency and adverse reaction rate, the treatment group was better than the control group. There was a statistical difference (P < 0.05); a total of 559 chemical constituents and 2306 potential targets were obtained from the online database. Of these, 201 components, 145 targets, and 185 pathways were closely related to cerebral infarction. CONCLUSIONS: The available evidence indicates that the addition of Zhishe Tongluo capsule to the conventional treatment of Western medicine can improve the clinical efficacy of cerebral infarction and has some advantages in regulating blood lipids and hemorheology, but the overall evidence level is low, which still needs to be further supported by large-scale and multicenter RCTs; intervention of brain infarction by Zhishe Tongluo capsule is a comprehensive result of multicomponent and multi-target interactions. On the basis of the combined meta-analysis and network pharmacology in scientific attempts, it also provides a reference for the clinical evaluation of other drugs and mechanism research.

Neuroprotective effects of synthetic borneol and natural borneol based on the neurovascular unit against cerebral ischaemic injury.

OBJECTIVES: Natural borneol and synthetic borneol were commonly used to treat ischaemic stroke in clinical practice. This study evaluated their different neuroprotective effects on the remodelling and repair of the neurovascular unit (NVU) after cerebral ischaemia. METHODS: We evaluated the different effects of borneol through neurological test and staining methods in cerebral ischaemia injury. Western blot, immunohistochemistry and transmission electron microscopy were used to evaluate the reparative effects of borneol on NVU. KEY FINDINGS: The prevention and treatment of borneol could prolong recovery time, reduce body temperature and cerebral infarction rate and improve pathological conditions. Further investigations revealed that borneol could inhibit the expression of DII4, Hes1, Hes5 and p65 and increase the Nissl body number and microvessel density. They also inhibited the activation of the microglia. It was also observed through an ultramicroelectron microscope that the structural stability of the NVU has also been repaired. Moreover, natural borneol shows better results in most indicators when compared with synthetic borneol. CONCLUSIONS: Natural borneol showed a stronger effectiveness and had better regulation and neuroprotection on the NVU when compared with synthetic borneol, indicating that it may be better to use natural borneol in the prescription of Chinese patent medicine in clinical practice.

Highly Diastereoselective Synthesis of Tetrahydroquinoline Derivatives via [4 + 2] Annulation of Ortho-Tosylaminophenyl-Substituted Para-Quinone Methides and Cyanoalkenes.

As a privileged structural motif, tetrahydroquinoline skeletons widely exist in biologically active natural products and pharmaceuticals. In this protocol, a highly diastereoselective [4 + 2] annulation of ortho-tosylaminophenyl-substituted p-QMs and cyanoalkenes to construct tetrahydroquinoline derivatives has been successfully achieved. This strategy proceeds efficiently under mild condition, offering straightforward route to a variety of 4-aryl-substituted tetrahydroquinolines with high yields, excellent diastereoselectivities, broad functional group tolerance as well as gram-scale capacity. Moreover, a one-pot reaction sequence utilizing in situ generated p-QMs under the similar condition to build tetrahydroquinoline framework is smoothly conducted with good reaction performance as well as step and atom economy.

Investigation of anti-osteoporosis mechanisms of Rehmanniae Radix Preparata based on network pharmacology and experimental verification.

BACKGROUND: Rehmanniae Radix Preparata (RRP) can effectively improve the symptoms of osteoporosis, but its molecular mechanism for treating osteoporosis is still unclear. The objective of this study is to investigate the anti-osteoporosis mechanisms of RRP through network pharmacology. METHODS: The overlapping targets of RRP and osteoporosis were screened out using online platforms. A visual network diagram of PPI was constructed and analyzed by Cytoscape 3.7.2 software. Molecular docking was used to evaluate the binding activity of ligands and receptors, and some key genes were verified through pharmacological experiments. RESULTS: According to topological analysis results, AKT1, MAPK1, ESR1, and SRC are critical genes for RRP to treat osteoporosis, and they have high binding activity with stigmasterol and sitosterol. The main signal pathways of RRP in the treatment of osteoporosis, including the estrogen signaling pathway, HIF-1 signal pathway, MAPK signal pathway, PI3K-Akt signal pathway. Results of animal experiments showed that RRP could significantly increase the expression levels of Akt1, MAPK1, ESR1, and SRC1 mRNA in bone tissue to increase bone density. CONCLUSION: This study explained the coordination between multiple components and multiple targets of RRP in the treatment of osteoporosis and provided new ideas for its clinical application and experimental research.

Network pharmacology and molecular docking reveal the effective substances and active mechanisms of Dalbergia Odoriferain protecting against ischemic stroke.

Dalbergia Odorifera (DO) has been widely used for the treatment of cardiovascular and cerebrovascular diseasesinclinical. However, the effective substances and possible mechanisms of DO are still unclear. In this study, network pharmacology and molecular docking were used toelucidate the effective substances and active mechanisms of DO in treating ischemic stroke (IS). 544 DO-related targets from 29 bioactive components and 344 IS-related targets were collected, among them, 71 overlapping common targets were got. Enrichment analysis showed that 12 components were the possible bioactive components in DO, which regulating 9 important signaling pathways in 3 biological processes including 'oxidative stress' (KEGG:04151, KEGG:04068, KEGG:04915), 'inflammatory response'(KEGG:04668, KEGG:04064) and 'vascular endothelial function regulation'(KEGG:04066, KEGG:04370). Among these, 5 bioactive components with degree≥20 among the 12 potential bioactive components were selected to be docked with the top5 core targets using AutodockVina software. According to the results of molecular docking, the binding sites of core target protein AKT1 and MOL002974, MOL002975, and MOL002914 were 9, 8, and 6, respectively, and they contained 2, 1, and 0 threonine residues, respectively. And some binding sites were consistent, which may be the reason for the similarities and differences between the docking results of the 3 core bioactive components. The results of in vitro experiments showed that OGD/R could inhibit cell survival and AKT phosphorylation which were reversed by the 3 core bioactive components. Among them, MOL002974 (butein) had a slightly better effect. Therefore, the protective effect of MOL002974 (butein) against cerebral ischemia was further evaluated in a rat model of middle cerebral artery occlusion (MCAO) by detecting neurological score, cerebral infarction volume and lactate dehydrogenase (LDH) level. The results indicated that MOL002974 (butein) could significantly improve the neurological score of rats, decrease cerebral infarction volume, and inhibit the level of LDH in the cerebral tissue and serum in a dose-dependent manner. In conclusion, network pharmacology and molecular docking predicate the possible effective substances and mechanisms of DO in treating IS. And the results are verified by the in vitro and in vivo experiments. This research reveals the possible effective substances from DO and its active mechanisms for treating IS and provides a new direction for the secondary development of DO for treating IS.

Tongxinluo Capsule Combined with Atorvastatin for Coronary Heart Disease: A Systematic Review and Meta-Analysis.

INTRODUCTION: Coronary heart disease (CHD) is a common clinical cardiovascular disease, and its morbidity and mortality rates are increasing, which brings a serious burden to the family and society. Dyslipidemia is one of the most important risk factors for CHD. However, it is difficult to reduce blood lipids to an ideal state with the administration of a statin alone. Tongxinluo capsule (TXLC), as a Chinese patent medicine, has received extensive attention in the treatment of CHD in recent years. This systematic review and meta-analysis aim to provide evidence-based medicine for TXLC combined with atorvastatin in the treatment of CHD. OBJECTIVE: To evaluate systematically the effectiveness and safety of TXLC combined with atorvastatin in the treatment of CHD. METHODS: Seven English and Chinese electronic databases (PubMed, Cochrane Library, Embase, CNKI, VIP, CBM, and Wanfang) were searched from inception to January 2020, to search for randomized controlled trials (RCTs) on TXLC combined with atorvastatin in the treatment of CHD. Two researchers independently screened the literature according to the literature inclusion and exclusion criteria and performed quality assessment and data extraction on the included RCTs. We performed a systematic review following Cochrane Collaboration Handbook and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and using a measurement tool to assess the methodological quality of systematic reviews (AMSTAR 2). The quality of outcomes was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). And meta-analysis was performed by Review Manager 5.2. RESULTS: A total of 15 RCTs with 1,578 participants were included in this review. Compared to atorvastatin treatment, TXLC combined with atorvastatin treatment showed potent efficacy when it came to the effectiveness of clinical treatment (RR = 1.24; 95% CI, 1.18, 1.29; P < 0.00001), total cholesterol (TC; MD = -1.21; 95% CI, -1.53, -0.89; P < 0.00001), triacylglycerol (TG; MD = -0.73; 95% CI, -0.81, -0.65; P < 0.00001), high-density lipoprotein cholesterol (HDL-C; MD = 0.27; 95% CI, 0.23, 0.31; P < 0.00001), low-density lipoprotein cholesterol (LDL-C; MD = -0.72; 95% CI, -0.80, -0.64; P < 0.00001), C-reactive protein (CRP; SMD = -2.06; 95% CI, -2.56, -1.57; P < 0.00001), frequency of angina pectoris (SMD = -1.41; 95% CI, -1.97, -0.85; P < 0.00001), duration of angina pectoris (MD = -2.30; 95% CI, -3.39, -1.21; P < 0.0001), and adverse reactions (RR = 0.84; 95% CI, 0.51, 1.39; P=0.50). No serious adverse events or reactions were mentioned in these RCTs. According to the PRISMA guidelines, although all studies were not fully reported in accordance with the checklist item, the reported items exceeded 80% of all items. With the AMSTAR 2 standard, the methodological quality assessment found that 9 studies were rated low quality and 6 studies were rated critically low quality. Based on the results of the systematic review, the GRADE system recommended ranking method was used to evaluate the quality of evidence and the recommendation level. The results showed that the level of evidence was low, and the recommendation intensity was a weak recommendation. CONCLUSIONS: TXLC combined with atorvastatin in the treatment of CHD can effectively improve the effectiveness of clinical treatment, significantly reduce the frequency and duration of angina pectoris, decrease blood lipids, and improve inflammatory factors. However, due to the low quality of the literature included in these studies and the variability of the evaluation methods of each study, there is still a need for a more high-quality, large sample, multicenter clinical randomized control for further demonstration.

Meta-Analysis of Clinical Efficacy and Safety of Tripterygium wilfordii Polyglycosides Tablets in the Treatment of Chronic Kidney Disease.

OBJECTIVE: Tripterygium wilfordii polyglycosides tablet (TGt) is an oral preparation extracted from plant Tripterygium wilfordii. It has the effects of anti-inflammation and inhibition of cellular and humoral immunity. However, many reports of adverse reactions caused by TGt have limited its application. In this paper, the clinical efficacy and safety of TGt in the treatment of chronic kidney disease (CKD) were verified by data mining and analysis, so as to provide theoretical data support for the application and development of TGt. METHODS: A computer search of the following databases was conducted: PubMed, Web of Science, CBM, VIP, Wanfang Data, and CNKI. The search time limit is from the establishment of the database to September 2020. We searched for clinical randomized controlled trials of TGt in the treatment of CKD. The main types of CKD involved are nephrotic syndrome (NS), primary nephrotic syndrome (PNS), refractory nephrotic syndrome (RNS), and IgA nephropathy (IgAN). RevMan 5.2 and Stata 12.0 software were used to evaluate the literature quality and analyze the data. Finally, GRADEpro software was used to evaluate the quality of evidence. RESULTS: According to the inclusion and exclusion criteria, 75 articles with a total of 6418 subjects were included. The results of the meta-analysis showed that TGt could reduce 24-hour urinary protein, increase serum albumin, improve clinical efficacy, and reduce disease recurrence rate in patients (P < 0.05) with CKD compared with adrenocortical hormones or immunosuppressants. TGt could significantly reduce the level of serum creatinine (Scr) in patients with CKD (P < 0.05), but it was not significant in reducing the level of blood urea nitrogen (P > 0.05). In terms of safety evaluation, in patients with CKD, it could significantly reduce the incidence of gastrointestinal adverse reactions and neurogenic dizziness and headache (P < 0.05). However, in terms of adverse reactions such as liver injury, respiratory infection, and leukopenia, TGt was as harmful as corticosteroids or immunosuppressants (P < 0.05). The quality of the evidence was evaluated with GRADEpro software, and the results showed that TGt was strongly recommended for the treatment of CKD. CONCLUSION: TGt has certain efficacy in the treatment of CKD and has fewer side effects in certain types of diseases. The effect of TGt combined with other drugs is better than that of single use. This paper also has some limitations. Due to the limited number of the included studies, with all being from China, there may be methodological differences. Therefore, more high-quality literature data from different countries are needed.