Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome.

The evidence for sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of type 2 diabetes or chronic heart failure was sufficient but lacking in acute coronary syndrome (ACS). Our aim was to investigate the effects of SGLT2i on cardiovascular outcomes in ACS patients. Studies of SGLT2i selection in ACS patients were searched and pooled. Outcomes included all-cause death, adverse cardiovascular events, cardiac remodeling as measured by the left ventricular end-diastolic dimension (LVEDD) and left ventricular end-systolic dimension (LVESD), cardiac function as assessed by the left ventricular ejection fraction (LVEF) and NT-proBNP, and glycemic control. Twenty-four studies with 12,413 patients were identified. Compared to the group without SGLT2i, SGLT2i showed benefits in reducing all-cause death (OR 0.72, 95% CI [0.61, 0.85]), major adverse cardiovascular events (MACE) (OR 0.44, 95% CI [0.30, 0.64]), cardiovascular death (OR 0.66, 95% CI [0.54, 0.81]), heart failure (OR 0.52, 95% CI [0.44, 0.62]), myocardial infarction (OR 0.68, 95% CI [0.56, 0.83]), angina pectoris (OR 0.37, 95% CI [0.17, 0.78]), and stroke (OR 0.48, 95% CI [0.24, 0.96]). Results favored SGLT2i for LVEDD (MD -2.03, 95% CI [-3.29, -0.77]), LVEF (MD 3.22, 95% CI [1.71, 4.72]), and NT-proBNP (MD -171.53, 95% CI [-260.98, -82.08]). Thus, SGLT2i treatment reduces the risk of all-cause death and MACE and improves cardiac remodeling and function in ACS patients.

Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy.

Osteosarcoma is usually resistant to immunotherapy and, thus primarily relies on surgical resection and high-dosage chemotherapy. Unfortunately, less invasive or toxic therapies such as photothermal therapy (PTT) and chemodynamic therapy (CDT) generally failed to show satisfactory outcomes. Adequate multimodal therapies with proper safety profiles may provide better solutions for osteosarcoma. Herein, a simple nanocomposite that synergistically combines CDT, PTT, and chemotherapy for osteosarcoma treatment was fabricated. In this composite, small 2D NiFe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil (5-FU) with high loading capacity. The nanospheres were then adsorbed onto larger 2D Ti3C2 MXene monolayers and finally shielded by bovine serum albumin (BSA) to form 5-FU@NiFe-LDH/Ti3C2/BSA nanoplatforms (5NiTiB). Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy, NiFe-LDH driven chemodynamic effects, and MXene-based photothermal killing collectively exhibited a synergistic "all-in-one" anti-tumor effect. 5NiTiB improved tumor suppression rate from <5% by 5-FU alone to ∼80.1%. This nanotherapeutic platform achieved higher therapeutic efficacy with a lower agent dose, thereby minimizing side effects. Moreover, the composite is simple to produce, enabling the fine-tuning of dosages to suit different requirements. Thus, the platform is versatile and efficient, with potential for further development.

Tremella fuciformis Polysaccharide Induces Apoptosis of B16 Melanoma Cells via Promoting the M1 Polarization of Macrophages.

Anti-tumor activity of Tremella fuciformis polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.

[Meta-analysis and GRADE evaluation of Guanxinning Tablets in treatment of angina pectoris of coronary heart disease].

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.

Dendrobium candidum polysaccharide reduce atopic dermatitis symptoms and modulate gut microbiota in DNFB-induced AD-like mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a high prevalence worldwide. Increasing evidence suggests that the gut microbiota plays an important role in the pathogenesis of AD. In this study, we sought to verify the effect of Dendrobium candidum polysaccharides (DCP) on AD induced by 2,4-Dinitrofluorobenzene (DNFB) in Balb/c mice regarding its impact on the intestinal microbiome. We found that 2-week oral administration of DCP improved AD-like symptoms and histological damage of skin, reduced mast cell infiltration, down-regulated the level of serum total IgE and the expression of pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-4 and IL-6, and increased the expression level of anti-inflammatory cytokine IL-10. The beneficial effect of DCP was attributed to the restoration of the intestinal microbiome composition and the unbalance of the intestinal homeostasis. Our results indicated that DCP might be used as a promising novel microbiota-modulating agent for the treatment of AD.

Live Macrophage-Delivered Doxorubicin-Loaded Liposomes Effectively Treat Triple-Negative Breast Cancer.

Triple-negative breast cancer is often aggressive and resistant to various cancer therapies, especially corresponding targeted drugs. It is shown that targeted delivery of chemotherapeutic drugs to tumor sites could enhance treatment outcome against triple-negative breast cancer. In this study, we exploited the active tumor-targeting capability of macrophages by loading doxorubicin-carrying liposomes on their surfaces via biotin-avidin interactions. Compared with conventional liposomes, this macrophage-liposome (MA-Lip) system further increased doxorubicin accumulation in tumor sites, penetrated deeper into tumor tissue, and enhanced antitumor immune response. As a result, the MA-Lip system significantly lengthened the survival rate of 4T1 cell-bearing mice with low toxicity. Besides, the MA-Lip system used highly biocompatible and widely approved materials, which ensured its long-term safety. This study provides a system for triple-negative breast cancer treatment and offers another macrophage-based strategy for tumor delivery.

The Essential Oil Derived from Perilla frutescens (L.) Britt. Attenuates Imiquimod-Induced Psoriasis-like Skin Lesions in BALB/c Mice.

Psoriasis is reported to be a common chronic immune-mediated skin disease characterized by abnormal keratinocytes and cell proliferation. Perilla leaves are rich in essential oils, fatty acids, and flavonoids, which are recognized for their antioxidant and anti-inflammatory effects. In this study, the alleviating effect of essential oil (PO) extracted from Perilla frutescens stems and leaves on imiquimod (IMQ) -induced psoriasis-like lesions in BALB/c mice were investigated. Results showed that PO ameliorated psoriasis-like lesions in vivo, reduced the expression of lymphocyte antigen 6 complex locus G6D (Ly-6G), which is a marker of neutrophil activation, and inhibited the expression of inflammatory factors interleukin 1 (IL-1), interleukin 6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX2). In addition, PO significantly decreased the expression of cytokines such as IL-6, IL-1, interleukin 23 (IL-23), interleukin 17 (IL-17), and nuclear factor kappa-B (NF-κB). Furthermore, the down-regulation of mRNA levels of psoriasis-related pro-inflammatory cytokines, such as IL-17, interleukin 22 (IL-22), IL-23, interferon-α (IFN-α), and Interferon-γ (IFN-γ) was observed with the treatment of PO. All results show a concentration dependence of PO, with low concentrations showing the best results. These results suggest that PO effectively alleviated psoriasis-like skin lesions and down-regulated inflammatory responses, which indicates that PO could potentially be used for further studies on inflammation-related skin diseases such as psoriasis and for the treatment of psoriasis such as psoriasis natural plant essential oil resources.

CircMYC promotes proliferation, migration, invasion and inhibits apoptosis of small cell lung cancer by targeting miR-145/ Matrix Metallopeptidase 2 axis.

Circular RNAs (circRNAs) are involved in the carcinogenesis of lung cancer. Human MYC gene is highly expressed in melanoma, multiple myeloma, and nasopharyngeal carcinoma. We aimed to investigate the role of circMYC in small cell lung cancer (SCLC). The expression of cirMYC in SCLC tissues and cells were examined. Functional studies were performed to evaluate the roles of circMYC in SCLC cells. Luciferase reporter gene assay, RNA pull-down assay, and rescue experiments were performed to evaluate the regulatory relationship between circMYC and miR-145, and MiR-145 and MMP2 mRNA. We found that CirMYC was highly expressed in SCLC tissues and cells. Knockdown of circMYC could inhibit cell proliferation, migration, invasion, and induce apoptosis. CircMYC targeted miR-145 and miR-145 targeted MMP2 (Matrix Metallopeptidase 2) mRNA. Our data indicated that circMYC upregulates the expression of MMP-2 by inhibiting miR-145, which functions to promote the proliferation, migration, and invasion and inhibit the apoptosis of SCLC. These findings suggest that targeting circMYC/miR-145/MMP-2 could serve as a potential therapeutic strategy for SCLC treatment.

Assessing the geographical distribution of 76 Dendrobium species and impacts of climate change on their potential suitable distribution area in China.

The geographical distribution of plant resources is of great significance for studying the origin, distribution, and evolution of species. Climate and geographical factors help shape the distribution of plant species. Dendrobium is a commonly used traditional medicine and a precious economic crop in China. Owing to the over-exploitation and increasing medicinal demand of Dendrobium species plants, systematic investigation of the geographical distribution of the plants and analysis of their potential distribution under climate change are important for protecting Dendrobium plants. We adopted DIVA-GIS to analyze the georeferenced records of 76 species of the Dendrobium species collected from 2166 herbarium records. We analyzed the eco-geographical distribution and species richness of the genus Dendrobium to simulate the distribution of current and future scenarios using MaxEnt. The results revealed the distribution of Dendrobium in 30 provinces of China, with species abundance in Yunnan, Guangxi, Guangdong, and Hainan. Our model identified the following bioclimatic variables: precipitation in the driest months and the warmest seasons, isothermality, and range of annual temperature. Among them, annual precipitation is the most crucial bioclimatic variable affecting the distribution of 16 selected Dendrobium species. The change of climate in the future will lead to an increase in habitat suitability for some Dendrobium species as follows: D. officinal 2.12%, D. hancockii by 6.00%, D. hercoglossum by 8.25%, D. devonianum by 7.71%, D. henryi by 9.40%, and D. hainanense by 13.70%. By contrast, habitat suitability will dramatically decrease for other Dendrobium species: D. chrysotoxum by 0.89%, D. chrysanthum by 12.68%, D. fimbriatum by 5.07%, D. aduncum by 11.44%, D. densiflorum by 18.47%, D. aphyllum by 8.05%, D. loddigesii by 16.45%, D. nobile by 5.41%, D. falconeri by 8.73%, and D. moniliforme by 10.61%. The reduction of these species will be detrimental to the medicinal and economic value of the genus Dendrobium. Therefore, targeted development and reasonable management strategies should be adopted to conserve these valuable resources.

Tight junction protein CLDN17 serves as a tumor suppressor to reduce the invasion and migration of oral cancer cells by inhibiting epithelial-mesenchymal transition.

OBJECTIVE: To investigate claudin-17 (CLDN17) expression in oral cancer and its effect on epithelial-mesenchymal transition (EMT), invasion and migration in oral cancer cells. METHODS: The GEO2R tool was used to analyze gene expression in two microarray datasets (GSE74530 and GSE146483) derived from the Gene Expression Omnibus (GEO) database. Gene Expression Profiling Interactive Analysis (GEPIA) verified CLDN17 expression in head and neck squamous cell carcinoma (HNSC) patients. Moreover, oral cancer cells were transfected with CLDN17 overexpression plasmid or CLDN17 shRNA to evaluate cell invasion and migration. Gene and protein expression was detected by qRT-PCR, immunohistochemistry and western blotting. RESULTS: CLDN17 was one of the top 200 differentially expressed genes in the GSE74530 and GSE146483 datasets and was downregulated in oral cancer. CLDN17 expression was higher in HNSC tissues, and it was related to TNM staging. In HNSC tumors, CLDN17 expression was positively correlated with CDH1 but negatively related to VIM, SNAIL1, SNAIL2, and TWIST1. Meanwhile, we found that CLDN17 expression was lower in oral cancer tissues; it declined with higher T status, N status, M status and staging, lower differentiation grade, and a worse prognosis. Upregulation of CLDN17 inhibited the invasion and migration of oral cancer cells, with elevated CDH1 and reduced VIM, SNAIL1, SNAIL2, and TWIST1, while CLDN17 downregulation had the opposite effects. CONCLUSION: CLDN17 may serve as a tumor suppressor in oral cancer since it could reduce the invasion and migration of cells by inhibiting the EMT process, thus becoming a potential therapeutic target in oral cancer.

The Central Response of Electroacupuncture on Trigeminal Neuralgia Based on Resting-State Functional Magnetic Resonance Imaging: A Protocol for a Pre-Experimental, Single-Centre, Randomized, Controlled Trial.

OBJECTIVE: To verify the efficacy of electroacupuncture (EA) on classical trigeminal neuralgia (CTN), and to observe the brain functional status of patients with CTN and the intervention effects of EA on brain function by resting-state functional magnetic resonance imaging (rs-fMRI). METHODS AND ANALYSIS: Thirty CTN patients will be randomly divided into EA combined with carbamazepine group and carbamazepine group in 2:1 ratio by using a random number table. Patients in EA combined with carbamazepine will receive EA treatment and carbamazepine for four weeks. The carbamazepine group will only receive carbamazepine treatment. VAS (visual analogue scale), HAMA (Hamilton Anxiety Scale), HAMD (Hamilton Depression Scale) and SF-36 (short form 36 health survey) will be performed before, after four-week treatments and at three-month follow-up in CTN patients. Six CTN patients will be randomly selected from EA combined with carbamazepine group and carbamazepine group, respectively, before treatment, and twelve paired healthy participants will be recruited at the same time. The twelve CTN patients will be scanned by rs-fMRI before and after treatment, and the healthy participants will be scanned by rs-fMRI only at baseline. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis will be carried out to compare the dysfunctional brain regions between CTN patients and healthy participants, as well as the differences between two groups of patients with CTN after treatment. TRIAL REGISTRATION: ChiCTR-1900027873.

[Preparation and in vitro evaluation of self-assembled beads drug delivery system of berberine hydrochloride].

The purpose of the present work was to investigate the innovative self-assembling system, "beads", prepared by continuously shaking alpha-cyclodextrin and soybean oil without the use of organic solvents and surfactants at room temperature. Berberine hydrochloride previously dissolved in soybean oil was chosen as a model drug to explore the shape, structure, drug loading and in vitro release of beads. The particle size and drug loading of berberine hydrochloride-loaded beads were (2.25 +/- 0.23) mm and (67.02 +/- 0.64) microg x g(-1), respectively. Confocal microscopy showed that the core-shell structure of beads could contain poorly water soluble drugs or lipophilic drugs in the lipid core. The drug release rate and cumulative releases of beads were both higher than those of raw medicine of berberine hydrochloride in simulated intestinal fluid. These results suggested that beads were the novel and potential lipid-based drug delivery system for lipophilic or poorly water soluble traditional Chinese medicine.