A Comprehensive Review of Bupleuri Radix and its Bioactive Components： with a Major Focus on Treating Chronic Liver Diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

Incorporating mesopelagic fish into the evaluation of conservation areas for marine living resources under climate change scenarios.

Mesopelagic fish (meso-fish) are central species within the Southern Ocean (SO). However, their ecosystem role and adaptive capacity to climate change are rarely integrated into protected areas assessments. This is a pity given their importance as crucial prey and predators in food webs, coupled with the impacts of climate change. Here, we estimate the habitat distribution of nine meso-fish using an ensemble model approach (MAXENT, random forest, and boosted regression tree). Four climate model simulations were used to project their distribution under two representative concentration pathways (RCP4.5 and RCP8.5) for short-term (2006-2055) and long-term (2050-2099) periods. In addition, we assess the ecological representativeness of protected areas under climate change scenarios using meso-fish as indicator species. Our models show that all species shift poleward in the future. Lanternfishes (family Myctophidae) are predicted to migrate poleward more than other families (Paralepididae, Nototheniidae, Bathylagidae, and Gonostomatidae). In comparison, lanternfishes were projected to increase habitat area in the eastern SO but lose area in the western SO; the opposite was projected for species in other families. Important areas (IAs) of meso-fish are mainly distributed near the Antarctic Peninsula and East Antarctica. Negotiated protected area cover 23% of IAs at present and 38% of IAs in the future (RCP8.5, long-term future). Many IAs of meso-fish still need to be included in protected areas, such as the Prydz Bay and the seas around the Antarctic Peninsula. Our results provide a framework for evaluating protected areas incorporating climate change adaptation strategies for protected areas management. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00188-9.

Network pharmacology and transcriptomic profiling elucidate the therapeutic effects of Ranunculus ternatus Thunb on liver fibrosis via MK3-NF-κB inhibition.

Activation of hepatic stellate cells (HSCs) is critical in the progression of liver fibrosis and is a promising target for anti-hepatic fibrosis drug development. Moreover, effective pharmacological interventions targeting this pathomechanism are scarce. Our study confirms the therapeutic value of ß-sitosterol, a major constituent of Ranunculus ternatus Thunb, in hepatic fibrosis and identifies its underlying mechanisms. After treatment with ß-sitosterol, CCL4-induced hepatic fibrosis was reversed in mice, while inflammatory and hepatic fibrosis indices were improved. Meanwhile, we explored the molecular mechanism of ß-sitosterol treatment for hepatic fibrosis and, based on RNA-seq results, found that the ameliorative effect of ß-sitosterol on hepatic fibrosis was associated with the MK3 and NF-κB signalling pathways. MK3, an important kinase in the MAPK pathway, plays a role in transmitting upstream and downstream signals, whereas the NF-κB signalling pathway has been shown to be associated with HSC activation. We verified the interaction between MK3 and IκB in HSC cells using endogenous Co-IP, whereas ß-sitosterol reduced the binding of MK3 to IκB and the activation of the NF-κB signalling pathway. Our findings reveal the mechanism of ß-sitosterol in the treatment of liver fibrosis, suggesting that ß-sitosterol may be a promising drug for the treatment of liver fibrosis and deserves further investigation.

Multi-interfacial bridging engineering of flexible MXene film for efficient electromagnetic shielding and energy conversion.

Accompanied by the progressive development of electronic equipment, excellent electromagnetic interference (EMI) shielding materials display a satisfying prospect in protecting electronic devices against electromagnetic pollution/radiation, while integrating energy conversion. Heretofore, it remains a conundrum to availably construct thin films with multi-interfacial bridging engineering as multifunctional shielding devices. To effectively achieve electromagnetic wave attenuation and integrate energy conversion, a co-mixed vacuum-assisted filtration strategy is designed to synthesize Au@MXene/cellulose nanocrystal/dodecylbenzenesulfonic acid-doped polyaniline (AMCP) films. Profited from the interfacial engineering, the total EMI shielding effectiveness (SE) can be increased by 27 % with the highest value of 67.9 dB. MXene with localized surface plasmon resonance characteristics gives the composite films good energy conversion performance, that is, the composite film can be rapidly heated up to 100 °C under the irradiation of an infrared lamp, and its surface temperature remains stable after continuous irradiation. Additionally, the infrared emissivity is as low as 0.173 within the 8-14 µm, which is necessary to adapt various application scenarios. Therefore, it is reliable that the AMCP films constructed by multicomponent offer a facile strategy for MXene-based EMI shielding devices with integration characteristics.

Delayed sternal Mycobacterium tuberculosis infection after left ventricular assist device implantation: A case report.

The incidence of Mycobacterium tuberculosis (Mtb) infection in patients with mechanical circulatory support devices is extremely rare. We present a case involving a 38-year-old male who experienced a delayed sternal Mtb infection following left ventricular assist device (LVAD) implantation. More than 5 months post-surgery, the patient was readmitted to the hospital presenting a subxiphoid abscess. The incision site displayed an unsatisfactory healing process after the incision and drainage of the abscess. Despite engaging in a rigorous treatment protocol, which included anti-infective therapy, vacuum-assisted closure, and surgical debridement, the patient's wound remained unhealed. Ultimately, after pus gene sequencing confirmed the diagnosis, the patient was administered a regimen combining anti-tuberculosis and anti-infective therapy, which culminated in the successful healing of the wound. This singular case study not only reveals the clinical progression of an unexpected Mtb infection post-implantation but also emphasizes the challenges encountered in diagnosis and management.

RAD54B promotes gastric cancer cell migration and angiogenesis via the Wnt/ß-catenin pathway.

BACKGROUND: Gastric cancer is an epidemic malignancy that is commonly diagnosed at the late stage. Evidence has elucidated that RAD54B exerts a crucial role in the progress of various tumors, but its specific role and mechanism in gastric cancer remain gloomy. MATERIALS AND METHODS: The level of RAD54B was detected by western blot. RAD54B expression was downregulated or upregulated in both MKN45 and AGS cells by the transfection of shRAD54B or overexpression plasmid, respectively. The role of RAD54B in the growth, migration, invasion and tube formation of gastric cancer was evaluated by Edu, colony formation, transwell and tube formation assays. In addition, the molecular mechanism of RAD54B in gastric cancer was also determined by western blot. Moreover, in vivo experiment was conducted in xenografted mice. RESULTS: The expression of RAD54B was discovered to be upregulated in gastric cancer based on the ATGC and GEPIA databases, which was also confirmed in gastric cancer cell lines. Moreover, overexpression of RAD54B enhanced the growth, migration, invasion, tube formation and Wnt/ß-catenin signaling axis in AGS and MKN45 cells. As expected, knockdown of RAD54B in AGS and MKN45 cells reversed these promotions. More importantly, in vivo assay also verified that RAD54B accelerated the growth of gastric cancer and Wnt/ß-catenin signaling pathway. CONCLUSIONS: Both loss-of-function and gain-of-function assays demonstrated that RAD54B facilitated gastric cancer cell progress and angiogenesis through the Wnt/ß-catenin axis.

Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation.

BACKGROUND: Altered patterns of bile acids (BAs) are frequently present in liver fibrosis, and BAs function as signaling molecules to initiate inflammatory responses. Therefore, this study was conducted to uncover the notably altered components of BAs and to explore the pathway of altered BA induced inflammation in the development of liver fibrosis. METHODS: Bile acids were quantified by ultraperformance liquid chromatography coupled to mass spectrometry (UPLC‒MS/MS). Cell Counting Kit-8 assays were used to determine the proliferative capacity of HSCs. Transwell assays and wound healing assays were used to determine the migratory capacity of LX2 cells. Protein expression was evaluated by western blotting. RESULTS: Plasma bile acid analysis showed higher levels of GCDCA, TCDCA, GCA and TCA in patients with liver fibrosis than in normal controls. The AUC of GCDCA was the highest. Western blotting showed that GCDCA treatment increased the expression of NLRP3-related proteins and collagen1 in vitro and significantly increased LX2 cells proliferation and migration. Furthermore, knockdown of NLRP3 or overexpression of FXR in LX2 cells decreased the expression of the above proteins, and FXR inhibited NLRP3 (ser 295) phosphorylation in vitro and vivo. In vivo, HE, Masson's trichrome, and Sirius Red staining showed that GCDCA increased collagen fibers in the mouse liver, and the expression of NLRP3-related proteins, collagen 1, and α-SMA in the liver increased significantly. However, the knockout of NLRP3 reversed these patterns. CONCLUSION: (1) Primary conjugated bile acids increased in patients with liver fibrosis; (2) GCDCA induce hepatic fibrosis via the NLRP3 inflammasome pathway; (3) FXR inhibits NLRP3 activity by restraining its phosphorylation; (4) knockdown or knockout of NLRP3 may relieve the onset of hepatic fibrosis.

Tanc1/2 TPR domain interacts with Myo18a C-terminus and undergoes liquid-liquid phase separation.

Tanc1 and its homologous protein Tanc2 are critical synaptic scaffold proteins which regulate synaptic spine densities and excitatory synapse strength. Recent studies indicated TANC1 and TANC2 are candidate genes of several neurodevelopmental disorders (NDDs). In this study, we identified and characterized a novel interaction between Tanc1/2 and Myo18a, mediated by the Tanc1/2 TPR domains and Myo18a coiled-coil domain and C-extension (CCex). Sequence analysis and size exclusion chromatography experiments reveal that high salt disrupts the interaction between Myo18a and Tanc1/2, indicating that the interaction is primarily driven by charge-charge interactions. More importantly, we found that the Tanc1-TPR/Myo18a CCex interaction could undergo liquid-liquid phase separation (LLPS) in both cultured cells and test tubes, which provides the biochemical basis and potential molecular mechanisms for the LLPS-mediated interactions between Myo18a and Tanc1/2.

Research on multi-target data association of the infrared fish-eye warning system.

The multi-target data association method is studied in order to realize multi-target tracking in infrared fish-eye warning system. The Neural Joint Probabilistic Data Association (NJPDA) algorithm is analyzed. It is found that the NJPDA algorithm only considers the distance information between the measurement and the target in the data association process, and its tracking accuracy needs to be further improved. Therefore, a new method fused with direction information is proposed based on the NJPDA algorithm. The proposed algorithm defines the concept of direction difference, introduces the direction information of target motion, and modifies the likelihood function by Gaussian weighting method, so as to fuse the direction information of target motion into the calculation of data interconnection probability. Experimental results demonstrate that the tracking success rate of the proposed algorithm is nearly 10 % higher than that of JPDA and NJPDA algorithms and its consuming time meets the real-time requirement of the infrared fish-eye warning system.

Dynamic interactions between E-cadherin and Ankyrin-G mediate epithelial cell polarity maintenance.

E-cadherin is an essential cell‒cell adhesion protein that mediates canonical cadherin-catenin complex formation in epithelial lateral membranes. Ankyrin-G (AnkG), a scaffold protein linking membrane proteins to the spectrin-based cytoskeleton, coordinates with E-cadherin to maintain epithelial cell polarity. However, the molecular mechanisms governing this complex formation and its relationships with the cadherin-catenin complex remain elusive. Here, we report that AnkG employs a promiscuous manner to encapsulate three discrete sites of E-cadherin by the same region, a dynamic mechanism that is distinct from the canonical 1:1 molar ratio previously described for other AnkG or E-cadherin-mediated complexes. Moreover, we demonstrate that AnkG-binding-deficient E-cadherin exhibited defective accumulation at the lateral membranes and show that disruption of interactions resulted in cell polarity malfunction. Finally, we demonstrate that E-cadherin is capable of simultaneously anchoring to AnkG and ß-catenin, providing mechanistic insights into the functional orchestration of the ankyrin-spectrin complex with the cadherin-catenin complex. Collectively, our results show that complex formation between E-cadherin and AnkG is dynamic, which enables the maintenance of epithelial cell polarity by ensuring faithful targeting of the adhesion molecule-scaffold protein complex, thus providing molecular mechanisms for essential E-cadherin-mediated complex assembly at cell‒cell junctions.

Sclerotome-derived PDGF signaling functions as a niche cue responsible for primitive erythropoiesis.

Primitive erythropoiesis serves a vital role in embryonic development, generating primitive red blood cells responsible for transportation of oxygen throughout the body. Although diverse niche factors are known to function in definitive hematopoiesis, the microenvironment contributing to primitive hematopoiesis remains largely elusive. Here, we report that platelet-derived growth factor (PDGF) signaling is required for erythroid progenitor differentiation in zebrafish. Ablating pdgfαa (also known as pdgfaa) and pdgfαb (also known as pdgfab) or blocking PDGF signaling with an inhibitor impairs erythroid progenitor differentiation, thus resulting in a significant decrease in the number of erythrocytes. We reveal that pdgfαb is expressed in sclerotomal cells, and that its receptor genes, pdgfra and pdgfrb, are expressed in the adjacent erythroid progenitor cells. Sclerotome-specific overexpression of pdgfαb effectively restores primitive erythropoiesis in pdgfαa-/-;pdgfαb-/- mutant embryos. In addition, we have defined ERK1/2 signaling as a downstream pathway of PDGF signaling during embryonic erythropoiesis. Taken together, our findings indicate that PDGF signaling derived from sclerotome functions as a niche cue for primitive erythropoiesis.

SASH1: A Novel Eph Receptor Partner and Insights into SAM-SAM Interactions.

The Eph (erythropoietin-producing human hepatocellular) receptor family, the largest subclass of receptor tyrosine kinases (RTKs), plays essential roles in embryonic development and neurogenesis. The intracellular Sterile Alpha Motif (SAM) domain presents a critical structural feature that distinguishes Eph receptors from other RTKs and participates in recruiting and binding downstream molecules. This study identified SASH1 (SAM and SH3 domain containing 1) as a novel Eph receptor-binding partner through SAM-SAM domain interactions. Our comprehensive biochemical analyses revealed that SASH1 selectively interacts with Eph receptors via its SAM1 domain, displaying the highest affinity for EphA8. The high-resolution crystal structure of the EphA8-SASH1 complex provided insights into the specific intermolecular interactions between these proteins. Cellular assays confirmed that EphA8 and SASH1 co-localize and co-precipitate in mammalian cells, with cancer mutations (EphA8 R942H or G978D) impairing this interaction. We demonstrated that SAM-SAM interaction is critical for SASH1-mediated regulation of EphA8 kinase activity, shedding new light on the Eph signaling pathway and expanding our understanding of the molecular basis of the tumor suppressor gene SASH1.

Recent Progress in Extracellular Vesicle-Based Carriers for Targeted Drug Delivery in Cancer Therapy.

Extracellular vesicles (EVs) are small, membrane-based vesicles released by cells that play a critical role in various physiological and pathological processes. They act as vehicles for transporting a variety of endogenous cargo molecules, enabling intercellular communication. Due to their natural properties, EVs have emerged as a promising "cell-free therapy" strategy for treating various diseases, including cancer. They serve as excellent carriers for different therapeutics, including nucleic acids, proteins, small molecules, and other nanomaterials. Modifying or engineering EVs can improve the efficacy, targeting, specificity, and biocompatibility of EV-based therapeutics for cancer therapy. In this review, we comprehensively outline the biogenesis, isolation, and methodologies of EVs, as well as their biological functions. We then focus on specific applications of EVs as drug carriers in cancer therapy by citing prominent recent studies. Additionally, we discuss the opportunities and challenges for using EVs as pharmaceutical drug delivery vehicles. Ultimately, we aim to provide theoretical and technical support for the development of EV-based carriers for cancer treatment.

Early life history affects fish size mainly by indirectly regulating the growth during each stage: a case study in a demersal fish.

The complex life histories of demersal fishes are artificially separated into multiple stages along with changes in morphology and habitat. It is worth exploring whether the phenotypes expressed earlier and later during the life cycle are related or decoupled. The life stages of first year Pacific cod (Gadus macrocephalus) were tracked over different hatch years and regions to test whether the early life history had a long-lasting effect on subsequent growth. We further explored the contribution of growth in the early and subsequent life history stages to body size at the end of each stage. In addition to the accessory growth centre and the first annual ring, the other two checks on the otolith possibly related to settlement and entering deeper waters were identified in 75 Pacific cod individuals. The direct and indirect relationships among the life history stages was interpreted based on path analysis. The results showed that growth prior to the formation of the accessory growth centre had a significant effect on the absolute growth of the fish before and after settlement and migration to deep water. However, there was no or moderate evidence that early growth affected the body size at each stage, which was mainly regulated by growth during the stage. This study supports the lasting effect of early growth and clarifies that it affects size mainly by indirectly regulating staged growth. Quantifying the phenotype relationships and identifying the internal mechanisms form the basis for assessing population dynamics and understanding the processes behind the changes. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00145-y.

Bacterial outer membrane vesicles-cloaked modified zein nanoparticles for oral delivery of paclitaxel.

To improve the aqueous solubility and oral bioavailability of paclitaxel (PTX), a biomimetic system for oral administration of PTX was efficiently developed as an outer membrane vesicle (OMVs) of sodium caseinate (CAS) modified zein nanoparticles (OMVs-Zein-CAS-PTX-NPs) by Escherichia coli. To verify their structure and properties, the designed nanostructures were thoroughly characterized using various characterization techniques. The results indicated that hydrogen bonds and van der Waals forces mainly drove the interaction between PTX and Zein, but the complex is unstable. The physicochemical stability of PTX-loaded zein nanoparticles was improved by the addition of CAS. The biological characteristics of biofilms are reproduced by nanoparticles cloaked with outer membrane vesicles. OMVs-Zein-CAS-PTX-NPs delayed the release of PTX under simulated gastric and intestinal fluids due to OMVs protection. OMVs-Zein-CAS-PTX-NPs exhibited remarkable antitumor ability in vitro and improved the bioavailability of oral administration of PTX in vivo. Therefore, OMVs cloaked in nanoparticles may be a suitable delivery vehicle to provide an efficient application prospect for the oral administration of PTX.

Liquid-liquid phase separation in hair cell stereocilia development and maintenance.

As an emerging concept, liquid-liquid phase separation (LLPS) in biological systems has shed light on the formation mechanisms of membrane-less compartments in cells. The process is driven by multivalent interactions of biomolecules such as proteins and/or nucleic acids, allowing them to form condensed structures. In the inner ear hair cells, LLPS-based biomolecular condensate assembly plays a vital role in the development and maintenance of stereocilia, the mechanosensing organelles located at the apical surface of hair cells. This review aims to summarize recent findings on the molecular basis governing the LLPS of Usher syndrome-related gene-encoding proteins and their binding partners, which may ultimately result in the formation of upper tip-link density and tip complex density in hair cell stereocilia, offering a better understanding of this severe inherited disease that causes deaf-blindness.

Structure of the N-terminal coiled-coil domains of the ciliary protein Rpgrip1l.

Rpgrip1l is one of the key ciliary proteins located at the transition zone of the primary cilium, an important organelle for cells to sense the outer environment. Mutations in the RPGRIP1L gene are associated with various ciliopathies. Here, we focused on the N-terminal coiled-coil of Rpgrip1l. By comprehensive biochemical and structural characterizations, we demonstrated that the two predicted coiled-coil regions (CC12) located at Rpgrip1l N-terminus each can form a stable parallel dimer. We further showed that overexpression of Rpgrip1l CC12 in NIH/3T3 cells significantly shortened the length of primary cilia, and this effect depended on the dimer formation. In addition, we found that CC12 of the homolog protein Rpgrip1 in mouse and human were significantly different from Rpgrip1l. Finally, we confirmed that some disease-related mutations can alter the dimeric states of CC12 of Rpgrip1l or Rpgrip1, which might explain the pathogenic mechanisms.

Climate risks to fishing species and fisheries in the China Seas.

Climate change is one of the most concerning topics in the Anthropocene. Increasing sea water temperature will trigger a series of ecological consequences, altering the various functions and services that marine ecosystems provide for humans. Fisheries, specifically, will likely face the most direct impact. China provides unparalleled catches with enormous and intensive fishing effort, and China Seas are suffering from significantly increasing water temperature. However, uncertainties in the impacts of climate change on fishing species and fisheries in the China Seas present challenges for the formulation of coping and adapting strategies. Here, we employed a climate risk assessment framework to evaluate the climate risks of fishing species and fisheries of various provinces in China in the past decade, aiming to benefit the development and prioritization of appropriate adaptation options to climate change. Results show that considering the water temperature in the 2010s, 20 % of fishing species in the China Seas have one-fourth of their habitats unsuitable, and the situation will become worse with future warming scenarios in the 2050s when nearly half of species will have at least one-fourth of their habitats no longer suitable. Integrating hazard, exposure and vulnerability, climate risks to fisheries feature heterogeneity among provinces. Climate risks to fisheries of northern provinces are characterized by low hazard and high exposure, while the southern counterparts are largely determined by high hazard and low exposure. Climate change is threatening fishing species and remarkably altering fishery patterns in China Seas. Shifting fishing targets, increasing fishing efficiency, raising catch diversity, and updating fishery-related industries would be effective steps to help fisheries adapt to climate change, and adaptation strategies need to be tailored considering local realities.

Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. AIM OF THE STUDY: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. MATERIALS AND METHODS: The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. RESULTS: Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. CONCLUSION: The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Efficacy and safety of Shouhui Tongbian Capsules in the treatment of constipation: A systematic review and meta-analysis.

BACKGROUND: Constipation is a common gastrointestinal disorder, which has seriously affected the quality of people's daily life. Traditional Chinese Medicine (TCM) therapy takes syndrome differentiation and treatment as the theoretical guidance with certain advantages in treating constipation with the holistic approach. However, there are few studies on the treatment of constipation with Shouhui Tongbian Capsules (SHTB). PURPOSE: This study was aimed to evaluate the clinical effect and safety of SHTB in the treatment of constipation and provide evidence-based references for clinical application. STUDY DESIGN: A systematic review and meta-analysis of existing literature on SHTB for treating constipation. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database) and English databases (PubMed, EmBase and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on SHTB for constipation from the establishment of all databases to September 26, 2022. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria and a meta-analysis was performed for selected data using Review Manager 5.4, ROB 2.0 and Stata 17.0. RESULTS: A total of 14 RCTs (randomized controlled trial) including 1310 participants were included in the analysis. The results showed that the test group was superior to the control group in improving the total effective rate and curative effect, clinical symptom score, gastrointestinal peptide index and reducing adverse reactions and recurrence rate. The specific results were as follows: ① The total effective rate increased significantly (RR = 1.24, 95% CI [1.18, 1.30], Z = 8.25, p< 0.00001); ② The clinical symptom indexs, including the difficulty of defecation [SMD = -1.28, 95% CI (-1.44, -1.12), Z = 15.65, p< 0.00001], the frequency of spontaneous defecation [SMD = 1.28, 95% CI (1.01, 1.54), Z = 9.52, p< 0.00001], defecation interval [SMD = -1.47, 95% CI (-1.68, -1.26), Z = 13.79, p < 0.00001], incomplete defecation [SMD = -1.34, 95% CI (-1.57, -1.11), Z = 11.42, p < 0.00001], duration of defecation [SMD = -2.02, 95% CI (-2.39, -1.65), Z = 10.73, p < 0.00001], stool characteristics [SMD = -2.30, 95% CI (-2.60, -1.99), Z = 14.72, p< 0.00001] and TCM main syndrome scores [SMD = -1.25, 95% CI (-1.46, -1.05), Z = 11.79, p< 0.00001] increased observably; ③ The gastrointestinal peptide hormone indexs, including MTL Level [SMD = 0.43, 95% CI (0.24, 0.62), Z = 4.44, p < 0.00001] and SP Level [RR =0.57, 95% CI (0.37, 0.87), Z = 2.61, p = 0.009] were improved obviously; ④ The incidence of adverse reactions (RR = 0.57, 95% CI [0.37, 0.87], Z = 2.61, p = 0.009) and recurrence rate (RR = 0.31, 95% CI [0.18, 0.54], Z = 4.28, P <0.001) reduced significantly. Sensitivity analysis showed that there was no significant change in all outcome indicators, which suggested that the results of meta-analysis were relatively stable. Funnel plot and Egger test results showed that the literature included in the study might have publication bias. CONCLUSION: SHTB can be used to treat functional constipation, especially elderly functional constipation, constipation caused by tumor chemotherapy and disease concomitant constipation. The optimal dosage of SHTB was 0.70 g (2 capsules) each time, 3 times a day, for 28 days. Combined with basic treatment, lactose oral solution, mosaic or castor oil could improve the total effective rate, clinical symptom indicators, gastrointestinal peptide hormone indicators and reduce adverse reaction rate of patients. However, due to the limitations of the included clinical trials, high-quality clinical trials with long follow ups are needed to evaluate the effectiveness and safety of SHTB in treating different types of constipation.