Highly precise strategy of polygalacturonic acid microcarriers functionalized with zwitterions and specific peptides for MSC screening.

Microcarriers for large-scale cell culture have a broader prospect in cell screening compared with the traditional high cost, low efficiency, and cell damaging methods. However, the equal biological affinity to cells has hindered its application. Therefore, based on the antifouling strategy of zwitterionic polymer, we developed a cell-specific microcarrier (CSMC) for shielding non-target cells and capturing mesenchymal stem cells (MSCs), which has characteristics of high biocompatibility, low background noise and high precision. Briefly, [2-(methacryloyloxy) ethyl] dimethyl-(3-sulfopropyl) ammonium hydroxide and glycidyl methacrylate were grafted onto polygalacturonic acid, respectively. The former built a hydration layer through solvation to provide an excellent antifouling surface, while the latter provided active sites for the click reaction with sulfhydryl-modified cell-specific peptides, resulting in rapid immobilization of peptides. This method is applicable to the vast majority of polysaccharide materials. The accurate capture ratio of MSCs by CSMC in a mixed multicellular environment is >95 % and the proliferation rate of MSCs on microcarriers is satisfactory. In summary, this grafting strategy of bioactive components lays a foundation for the application of polysaccharide materials in the biomedical field, and the specific adhesive microcarriers also open up new ideas for the development of stem cell screening as well.

Texture differences of microchambers and macrochambers in heel pads between the elderly with and without diabetes.

OBJECTIVE: This study aims to use the texture analysis of ultrasound images to distinguish the features of microchambers (a superficial thinner layer) and macrochambers (a deep thicker layer) in heel pads between the elderly with and without diabetes, so as to preliminarily explore whether texture analysis can identify the potential injury characteristics of deep tissue under the influence of diabetes before the obvious injury signs can be detected in clinical management. METHODS: Ultrasound images were obtained from the right heel (dominant leg) of eleven elderly people with diabetes (DM group) and eleven elderly people without diabetes (Non-DM group). The TekScan system was used to measure the peak plantar pressure (PPP) of each participant. Six gray-level co-occurrence matrix (GLCM) features including contrast, correlation, dissimilarity, energy, entropy, homogeneity were used to quantify texture changes in microchambers and macrochambers of heel pads. RESULTS: Significant differences in GLCM features (correlation, energy and entropy) of macrochambers were found between the two groups, while no significant differences in all GLCM features of microchambers were found between the two groups. No significant differences in PPP and tissue thickness in the heel region were observed between the two groups. CONCLUSIONS: In the elderly with diabetes who showed no significant differences in PPP and plantar tissue thickness compared to those without diabetes, several texture features of ultrasound images were found to be significantly different. Our finding indicates that texture features (correlation, energy and entropy) of macrochambers could be used for early detection of soft tissue damage associated with diabetes.

microRNA-181a-5p promotes fibroblast differentiation of mesenchymal stem cells in rats with pelvic floor dysfunction.

The use of stem cells capable of multilineage differentiation in treating Pelvic Floor Dysfunction (PFD) holds great promise since they are susceptible to entering connective tissue of various cell types and repairing damaged tissues. This research investigated the effect of microRNA-181a-5p (miR-181a-5p) on Bone Marrow Mesenchymal Stem Cells (BMSCs) in rats with PFD. BMSCs were transfected and analyzed for their fibroblast differentiation ability. miR-181a-5p, MFN1, and fibroblast-related genes were quantitatively analyzed. Whether MFN1 is a target gene of miR-181a-5p was predicted and confirmed. The efficacy of BMSCs in vivo rats with PFD was evaluated by measuring Leak Point Pressure (LPP), Conscious Cystometry (CMG), hematoxylin and eosin staining, and Masson staining. The present results discovered that miR-181a-5p was up-regulated and MFN1 was down-regulated during the differentiation of BMSCs into fibroblasts. Fibroblast differentiation of BMSCs was promoted after miR-181a-5p was induced or MFN1 was suppressed, but it was suppressed after miR-181a-5p was silenced. miR-181a-5p improved LPP and conscious CMG outcomes in PDF rats by targeting MFN1 expression, thereby accelerating fibroblast differentiation of BMSCs. In brief, miR-181a-5p induces fibroblast differentiation of BMSCs in PDF rats by MFN1, potentially targeting PDF therapeutics.

Correction: Incorporating mesopelagic fish into the evaluation of marine protected areas under climate change scenarios.

[This corrects the article DOI: 10.1007/s42995-023-00188-9.].

The different roles of V-ATPase a subunits in phagocytosis/endocytosis and autophagy.

Microglia are specialized macrophages responsible for the clearance of dead neurons and pathogens by phagocytosis and degradation. The degradation requires phagosome maturation and acidification provided by the vesicular- or vacuolar-type H+-translocating adenosine triphosphatase (V-ATPase), which is composed of the cytoplasmic V1 domain and the membrane-embedded Vo domain. The V-ATPase a subunit, an integral part of the Vo domain, has four isoforms in mammals. The functions of different isoforms on phagosome maturation in different cells/species remain controversial. Here we show that mutations of both the V-ATPase Atp6v0a1 and Tcirg1b/Atp6v0a3 subunits lead to the accumulation of phagosomes in zebrafish microglia. However, their mechanisms are different. The V-ATPase Atp6v0a1 subunit is mainly distributed in early and late phagosomes. Defects of this subunit lead to a defective transition from early phagosomes to late phagosomes. In contrast, The V-ATPase Tcirg1b/Atp6v0a3 subunit is primarily located on lysosomes and regulates late phagosome-lysosomal fusion. Defective Tcirg1b/Atp6v0a3, but not Atp6v0a1 subunit leads to reduced acidification and impaired macroautophagy/autophagy in microglia. We further showed that ATP6V0A1/a1 and TCIRG1/a3 subunits in mouse macrophages preferentially located in endosomes and lysosomes, respectively. Blocking these subunits disrupted early-to-late endosome transition and endosome-to-lysosome fusion, respectively. Taken together, our results highlight the essential and conserved roles played by different V-ATPase subunits in multiple steps of phagocytosis and endocytosis across various species.Abbrevations: Apoe: apolipoprotein E; ANXA5/annexin V: annexin A5; ATP6V0A1/a1: ATPase H+-transporting V0 subunit a1; ATP6V0A2/a2: ATPase H+-transporting V0 subunit a2; ATP6V0A4/a4: ATPase H+-transporting V0 subunit a4; dpf: days post-fertilization; EEA1: early endosome antigen 1; HOPS: homotypic fusion and protein sorting; LAMP1: lysosomal associated membrane protein 1; Lcp1: lymphocyte cytosolic protein 1 (L-plastin); Map1lc3/Lc3: microtubule-associated protein 1 light chain 3; NR: neutral red; PBS: phosphate-buffered saline; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; PtdIns(3,5)P2: phosphatidylinositol (3,5)-bisphosphate; RAB4: RAB4, member RAS oncogene family; RAB5: RAB5, member RAS oncogene family; RAB7: RAB7, member RAS oncogene family; TCIRG1/Atp6v0a3/a3: T cell immune regulator 1, ATPase H+-transporting V0 subunit a3; V-ATPase: vacuolar-type H+-translocating adenosine triphosphatase; Xla.Tubb2b/NBT: tubulin beta 2B class IIb.

Shouhui Tongbian Capsule in treatment of constipation: Treatment and mechanism development.

Constipation is common in the diseases of the digestive system in clinics. With the change in diet structure and the increase in life pressure, the prevalence rate increases year by year. In traditional Chinese medicine (TCM), the location of the disease of constipation is in the large intestine, which is related to the dysfunction of lung, spleen, liver, kidney and other viscera. Its pathogenesis is conductive dysfunction of large intestine. Based on the theory, Shouhui Tongbian Capsule (SHTB) is composed of eight traditional Chinese medicines, including Polygoni multiflori Radix (Heshouwu in Chinese), Aloe (Luhui in Chinese), Cassiae Semen (Juemingzi in Chinese), Ginseng Radix et Rhizoma (Renshen in Chinese), Lycii Fructus (Gouqizi in Chinese), Asini Corii Colla (Ejiao in Chinese), Aurantii Fructus Immaturus (Zhishi in Chinese), and Atractylodis Macrocephalae Rhizoma (Baizhu in Chinese), which could help to release excessive turbid, and nourishing yin and supplementing qi in the treatment. This study has been carried out to review the latest advances of SHTB in the treatment of constipation. The results showed that significant effect of SHTB was found in the treatment of constipation, such as functional constipation, and constipation associated with tumor chemotherapy, colitis, type 2 diabetes and chronic cardiac failure. Besides, obvious adverse reactions were not observed. SHTB could effectively treat five types of constipation, provide direction for the future exploration of SHTB in the treatment of other types of constipation.

[Installed strategy and clinical observation of self-made extracorporeal membrane oxygenation system in the treatment of critically ill patients].

OBJECTIVE: To summarize the strategy and method for the treatment of critically ill patients with self-made extracorporeal membrane oxygenation (ECMO) system. METHODS: A observative study was conducted. Fifty-six patients with ECMO assisted support in Fuwai Central China Cardiovascular Disease Hospital from December 2020 to December 2021 were enrolled. According to the clinical situation of the patients and the wishes of the family, conventional ECMO package (conventional group) or self-made ECMO package (self-made group) was chosen. In the conventional group, the disposable ECMO package was used to install the machine, pre charge and exhaust the air. In the self-made group, the disposable consumables commonly used in extracorporeal circulation during cardiac surgery (including centrifugal pump heads, membrane oxygenation, tubes, connectors, etc.) were used to create a self-made ECMO system. Based on the patient's situation, personalized tube model selection and length control were carried out. The preparation time, auxiliary time, auxiliary method, total pre charge volume, free hemoglobin (FHb) levels after 2 hours of ECMO operation and operating costs, as well as changes in hemodynamics, arterial blood gas analysis, and blood indicators within 48 hours after ECMO placement in the two groups were recorded. The occurrence of adverse events related to the ECMO system during ECMO adjuvant therapy in two groups was simultaneously observed. RESULTS: Fifty-six patients were enrolled finally, with 28 cases in the conventional group and 28 cases in the self-made group, and all successfully completed the operation of ECMO. There was no statistically significant difference in ECMO system preparation time, auxiliary time, auxiliary method, and FHb levels after 2 hours of ECMO operation between the conventional group and the self-made group [preparation time (minutes): 13±4 vs. 15±5, auxiliary time (hours): 287±34 vs. 276±42, veno-arterial ECMO (cases): 22 vs. 24, veno-venous ECMO (cases): 6 vs. 4, FHb after 2 hours of ECMO operation (mg/L): 226±67 vs. 253±78, all P > 0.05]. However, the total pre charge volume and operating costs in the self-made group were significantly lower than those in the conventional group [total pre charge volume (mL): 420±25 vs. 650±10, operating costs (ten thousand yuan): 3.8±0.4 vs. 6.7±0.3, both P < 0.01]. The hemodynamics, arterial blood gas analysis, and blood indicators of patients in the two groups were relatively stable within 48 hours after ECMO operation, and most of the indicators between the two groups showed no statistically significant differences. The hemoglobin (Hb) levels at 12, 24, and 48 hours after the machine transfer in the self-made group were significantly higher than those in the conventional group (g/L: 128.5±23.7 vs. 117.5±24.3 at 12 hours, 121.3±31.3 vs. 109.6±33.2 at 24 hours, 118.5±20.1 vs. 105.2±25.7 at 48 hours, all P < 0.05). Both groups of patients did not experience any adverse event related to the ECMO system, such as membrane pulmonary infiltration, joint detachment, and massive hemolysis, during the ECMO assisted treatment process. CONCLUSIONS: When implementing ECMO for critically ill patients in clinical practice, a self-made ECMO system with disposable consumables commonly used in extracorporeal circulation during cardiac surgery can be used for cardiopulmonary function assistance support, thereby saving patients medical costs and alleviating their dependence on disposable ECMO package in clinical practice.

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.

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.

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.