Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

Ethanol-Induced Hepatic Ferroptosis Is Mediated by PERK-Dependent MAMs Formation: Preventive Role of Quercetin.

SCOPE: Iron deposition is frequently observed in alcoholic liver disease (ALD), which indicates a potential role of ferroptosis in its development. This study aims to explore the effects of quercetin on ferroptosis in ALD and elucidates the underlying mechanism involving the formation of mitochondria-associated endoplasmic reticulum membranes (MAMs) mediated by protein kinase RNA-like endoplasmic reticulum kinase (PERK). METHODS AND RESULTS: C57BL/6J mice are fed either a regular or an ethanol-containing liquid diet (with 28% energy form ethanol) with or without quercetin supplementation (100 mg kg-1 BW) for 12 weeks. Ethanol feeding or treatment induced ferroptosis in mice and AML12 cells, which is associated with increased MAMs formation and PERK expression within MAMs. Quercetin attenuates these changes and protects against ethanol-induced liver injury. The antiferroptotic effect of quercetin is abolished by ferroptosis inducers, but mimicked by ferroptosis inhibitors and PERK knockdown. The study demonstrates that PERK structure, rather than its kinase activity (transfected with the K618A site mutation that inhibits kinase activity-ΔK plasmid or protein C terminal knockout-ΔC plasmid of PERK), mediates the enhanced MAMs formation and ferroptosis during the ethanol exposure. CONCLUSION: Quercetin ameliorates ethanol-induced liver injury by inhibiting ferroptosis via modulating PERK-dependent MAMs formation.

Research Status and Progress of Studies on Optic Disc Structures in Non-arteritic Anterior Ischemic Optic Neuropathy.

Objective: Non-arteritic anterior ischemic optic neuropathy (NAION) is a prevalent acute optic neuropathy. This article provides a comprehensive overview of the research advancements in regional optic disc structural changes and local risk factors among NAION patients, aiming to establish a foundation for clinical diagnosis, treatment, and future follow-up investigations. Methods: One English database and two Chinese databases were utilized for the purpose of conducting a comprehensive literature search, followed by meticulous analysis. The investigation encompassed an in-depth exploration of the optic disc's structural composition, as well as a thorough examination of the distinctive characteristics exhibited by NAION optic discs. Furthermore, this study aimed to elucidate the intricate relationship between NAION and ODD (Optic Disc Drusen) alongside PHOMS (Peripapillary Hyperreflective Ovoid Mass-like Structures). Results: A total of 44 English articles were retrieved from Pubmed, including case reports, clinical trials, and reviews. Keywords retrieved included NAION, optic disc, optic disc drusen, PHOMS. Conclusion: The risk factors of NAION include systemic factors such as hypertension, diabetes, and nocturnal hypotension and local factors such as small optic cup, crowded optic discs, ODD and PHOMS. Among them, ODD and PHOMS are the local anatomical changes of the optic disc, and their relationship with the occurrence of NAION has received more and more attention in recent years. NAION is more likely to occur in eyes with ODD and PHOMS, and NAION patients with ODD and PHOMS have a high prevalence. In recent years, optical coherence tomography (OCT) and optical coherence tomography angiography(OCTA) can provide accurate anatomical imaging and microvascular imaging. Help us better observe the local structural changes and local-related risk factors. Although ODD and PHOMS are closely associated with the occurrence and progression of NAION, research on their relationship is still in its nascent stages. Specifically, further investigation is needed to determine whether the presence of ODD and PHOMS affects the prognosis of NAION patients, including potential influences on lateral eye involvement.This article summarizes the changes in optic disc structure and local risk factors in NAION patients in order to clinical decision making in NIAON patients and provide a basis for further Research on the relationship between the occurrence of NIAON and optic disc structure.

Efficacy of Mometasone Furoate Cream Sodium Alginate Skin Repair Mask in Atopic Dermatitis Treatment.

Objective: To observe the clinical effect of mometasone furoate cream sodium Alginate Skin Repair Mask in the treatment of atopic dermatitis (AD). By assessing the combined use of these two treatments, the study aims to address a gap in knowledge regarding the effectiveness and safety of adjuvant therapies for AD, particularly in the context of Alginate Skin Repair Mask. Methods: Eighty patients were enrolled, including 42 males and 38 females aged 20-47 years, with an average age of (32.52±5.57) years, from July 2021 to July 2022, and the patients were divided into a single group (n=40) and a combined group (n=40) by random number table method. The patients in the single group were treated with mometasone furoate cream alone, and the patients in the combination group were treated with Alginate Skin Repair Mask on the basis of the treatment of the patients in the single group. The outcome measurements included clinical treatment effect, condition change (SCORAD score), quality of life (DLQI score), adverse reactions and disease recurrence were compared between the two groups. Both groups received treatment for 1 month. After the treatment of the patients, they were followed up for a period of 3 months. Results: The total effective rate of the single group was 80.0% (32/40), and that of the combined group was 97.5% (39/40) (P < .05). After treatment, the skin lesion area score, skin lesion degree score, pruritus insomnia score, and SCORAD total score in the combined group were significantly lower than those in the single group (35.03±9.41 vs 44.03±12.04) (all P < .05). The DLQI score of the combined group after treatment was significantly lower than that of the single group (3.72±1.53 vs 6.98±2.16) (P < .05). The incidence of adverse reactions in the single group was 22.5% (9/40), and the disease recurrence rate was 32.5% (13/40), while the incidence of adverse reactions in the combination group was 2.5% (1/40). The disease recurrence rate was 7.5% (3/40), and the incidence of adverse reactions and disease recurrence rate in the combination group were significantly lower than those in the single group (7.314, 7.812). Conclusion: Mometasone furoate cream sodium Alginate Skin Repair Mask has an ideal clinical effect in the treatment of atopic dermatitis. Compared with single mometasone furoate cream, the combination of sodium Alginate Skin Repair Mask can further improve the patient's condition, improve the quality of life of the patient, and reduce the risk of adverse reactions and disease recurrence. The higher total effective rate in the combined group indicates that the addition of Alginate Skin Repair Mask to the treatment regimen resulted in improved outcomes for patients with atopic dermatitis (AD). This translates to better control of the disease, reduction in symptoms, and overall improvement in the patient's condition.  However, it is important for clinicians to be aware that the use of topical glucocorticoids like mometasone furoate cream can potentially lead to adverse reactions. Some documented adverse reactions associated with long-term use of topical glucocorticoids include acne-like eruption, telangiectasia (dilation of small blood vessels), and local skin atrophy. By addressing multiple aspects of AD management, including skin barrier repair, moisturization, and inflammation control, the combination of mometasone furoate cream and Alginate Skin Repair Mask provides a more comprehensive treatment approach. This comprehensive approach may contribute to the observed reduction in recurrence rate in the combination group compared to the single group, where only mometasone furoate cream was used.

Teadenol B as a Component of Microorganism-Fermented Tea Extract Inhibited Breast Cancers by Promoting Autophagy.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Jianpi Antai formula prevents miscarriage by repressing M1 polarization of decidual macrophages through ubiquitination of NLRP3 mediated by MARCH7.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Antai Formula (JAF) is an ancient formula from He's gynecology, which has been used clinically for more than 30 years and has significant therapeutic effects on spontaneous abortion (SA). Both macrophage polarization and NLRP3 inflammasome correlate with the occurrence of SA in women with recurrent or threatened miscarriage. Whether JAF prevent SA via mediating activation of decidual macrophage (dMφ) and ubiquitination-associated degradation of NLRP3 remains uncertain. AIM OF THE STUDY: This study aimed to clarify the effects of JAF on pregnancy outcomes and dMφ polarization at the maternal-fetal interface in an SA mouse model, and use in vivo and invitro methods to explore whether JAF can inhibit M1 polarization of dMφ by up-regulating MARCH7-mediated NLRP3 ubiquitination, thereby preventing SA. MATERIALS AND METHODS: The CBA/J × DBA/2 mating method was used to establish an SA model and the dMφs of SA mice were isolated and cultured. Th1-, Th2-, Th17- and Treg-related cytokine levels were evaluated using ELISA. qRT-PCR was used to detect the levels of M1/M2 macrophage-related cytokine mRNA in the decidua, and western blotting was used to detect the expression of NLRP3 inflammasome-related proteins in the decidua and placenta. The expression of M1/M2 markers of dMφ was detected using flow cytometry, ASC speck formation was observed using immunofluorescence, and the ubiquitination level of MARCH7-NLRP3 was detected using co-immunoprecipitation. RESULTS: JAF increased the survival rate of fetuses and the levels of estradiol and progesterone in SA model mice. It also reduced the serum Th1 and Th17-associated cytokine levels and decidual M1 macrophage-associated cytokine levels, while elevating the M2 macrophages in SA mice. NLRP3, caspase-1, ASC, and IL-1ß protein expression in the decidua and placenta were also reduced. si-MARCH7 transfection reversed the effect of JAF on inhibiting the formation of the NLRP3 inflammasome and the activation of macrophages in dMφs of SA mice. CONCLUSION: JAF could effectively prevent and treat SA by repressing M1 polarization of dMφs through NLRP3 ubiquitination and pyroptosis inhibition, which were mediated by MARCH7.

Combination of Anti-PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable Colorectal Cancer.

Programmed death receptor-1 (PD-1) inhibitors are ineffective against microsatellite-stable (MSS) colorectal cancer. Electroacupuncture (EA) has oncosuppressive and immunomodulatory properties. Here, we investigated the antitumor effects of EA and explored the feasibility of EA combined with anti-PD-1 in MSS colorectal cancer. Results showed that EA exerted its antitumor effect in an intensity-specific manner, and moderate-intensity EA (1.0 mA) induced maximal tumor inhibition. EA enhanced antitumor immune responses by increasing lymphocytes and granzyme B (GzmB) levels, as well as activating the stimulator of IFN genes (STING) pathway. EA combined with anti-PD-1 showed superior efficacy compared with either monotherapy in multiple MSS colorectal cancer mouse models. Single-cell RNA sequencing revealed that cotreatment reprogrammed the tumor immune microenvironment (TIME), as characterized by enhancement of cytotoxic functions. Mechanically, we found that the potentiated effect of EA was dependent upon the STING pathway. Collectively, EA reshapes the TIME of MSS colorectal cancer and sensitizes tumors to anti-PD-1 in a STING pathway-dependent manner. These results provide a mechanistic rationale for using EA as an immunomodulatory strategy to improve the clinical efficacy of anti-PD-1 in MSS colorectal cancer. EA is safe, well-tolerated, and feasible for clinical translation as a promising strategy for treating MSS colorectal cancer.

Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.

Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.

Effects of curcumin on non-alcoholic fatty liver disease: A scientific metrogy study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases encountered in clinical practice. Curcumin can alleviate insulin resistance, inhibit oxidative stress response, reduce inflammation, reduce liver fat deposition, and effectively improve NAFLD through various modalities, inhibiting the progression into cirrhosis and fibrosis. PURPOSE: To explore the current status, hot spots, and developing trends of curcumin in NAFLD treatment through quantitative scientific analysis to serve as a reference for subsequent studies. STUDY DESIGN: A comprehensive analysis of the mechanism of action of curcumin in the treatment of NAFLD and methods to increase curcumin bioavailability using bibliometric analysis and literature review. METHODS: This study used VOSviewer software to analyze the literature related to curcumin treatment of NAFLD in the Web of Science (WOS) core set database. A comprehensive and in-depth review was conducted based on the results of scientific econometric research and literature review. RESULTS: The review observed that curcumin can activate various signaling pathways such as AMPK and NF-κB to inhibit oxidative stress and apoptosis, thereby reflecting its pharmacological effects: lowering lipid, anti-inflammatory, reducing insulin resistance, and anti-fibrosis. These mechanisms improve or even reverse the complex pathological features of lipid metabolism disorders associated with NAFLD. Curcumin also can potentially serve as a primary regulatory target for treating hepatic steatosis using gut microbiota. However, these pharmacological effects of curcumin were limited owing to its low bioavailability. CONCLUSION: This review discusses NAFLD treatment with curcumin, analyzes the reasons for its low bioavailability, and introduces models for studying and methods for improving curcumin bioavailability. As research on NAFLD grows, future research should capture the trend of basic research, pay attention to clinical research, and continuously explore the therapeutic potential of curcumin.

Danggui Buxue Decoction exerts its therapeutic effect on rheumatoid arthritis through the inhibition of Wnt/ß-catenin signaling pathway.

BACKGROUND: Danggui Buxue Decoction (DBD) is a traditional Chinese medicine prescription, which has the functions of benefiting Qi, generating blood and regulating the immune system. At present, various clinical reports suggest that DBD has some efficacy in Rheumatoid arthritis (RA), but its mechanism of action is still unclear. Thus, the present study explored mechanism of this preparation on RA. METHODS: The effect of DBD was evaluated by tumor necrosis factor (TNF)-α-induced Human fibroblast-like synoviocyte of rheumatoid arthritis (HFLS-RA) cell model and collagen-induced arthritis (CIA) rat model, respectively. Inflammatory factors including TNF-ɑ, IL-1ß, IL-6 and IL-10 in the culture supernatants or rat serum were measured using ELISA. The related indexes including fur luster, mental state and activity of rat and the symptoms including swelling and deformation of toes and ankles were also measured. RESULTS: In vitro results showed that DBD cannot only inhibit the proliferation of HFLS-RA cells but also reduce the levels of pro-inflammatory factors while increasing the level of anti-inflammatory factors. Similar results were obtained from in vivo experiments. Rats receiving DBD showed a decrease in the severity of rheumatoid arthritis in rat models. Moreover, the protein levels of c-myc and ß-catenin decreased significantly, while the protein level of SFRP4 increased, which indicated that DBD might inhibit the inflammatory reaction by regulating Wnt/ß-catenin signaling pathway, thus alleviating the symptoms of RA. CONCLUSION: Our findings not only provide insights for understanding the molecular mechanism of DBD in treating RA, but also provide the theoretical basis for further clinical prevention and treatment.

A Study on the Identification of High-Risk Factors and the Establishment of a Prediction Model for Uterine Rupture in an Unscarred Uterus During Pregnancy.

Objective: The diagnosis of uterine rupture was often delayed or misdiagnosed, leading to maternal morbidity and fetal mortality. The current study was performed to retrospectively identify high-risk factors of uterine rupture in an unscarred uterus (USU), and to establish a model to predict uterine rupture in USU during pregnancy. Methods: This was a retrospective multi-center study including five regional medical centers from the inception of each medical center to December 31 2021. Out of 547 325 deliveries, 28 patients with USU who had a uterine rupture during pregnancy were recruited. The following clinical characteristics were collected and analyzed: 1) general clinical characteristics; 2) clinical manifestations; 3) high-risk factors; 4) therapeutic strategies; 5) prognosis of mothers and infants. Results: In patients with a number of gravidities ≥2, the number of artificial abortions, the number of parities, and the amount of intraoperative blood loss were significantly increased (P = .002, .029, and .023). In patients with a previous history of artificial abortion, the number of parities, the probability of hysterectomy, and the incidence of intraoperative blood loss (>1000ml) were significantly increased (P < .001, .030 and .040, respectively). Additionally, multiparous patients had advanced maternal age, an increased number of gravidities, and a higher incidence of vaginal bleeding symptoms with significant differences (P = .042, .001, and .031). Based on the above results, we further developed a prediction model of uterine rupture in an unscarred uterus using Logistic binary regression analysis and the formula was as follows: Logit (P) = -9.112 + (-0.199) × maternal age + 0.374 × gestational age + 1.720 × parity + (-1.162) × number of artificial abortions. Conclusion: The number of gravidities ≥2, previous history of artificial abortion and multipara were associated with adverse outcomes in patients of uterine rupture in USU. A mathematical prediction formula was developed based on the parameters of maternal age, gestational age, number of parities, and number of artificial abortions. The risk of uterine rupture in USU can be predicted with two steps using formula I and formula II developed by us.

China Medicinal Plants of the Ampelopsis grossedentata-A Review of Their Botanical Characteristics, Use, Phytochemistry, Active Pharmacological Components, and Toxicology.

Ampelopsis grossedentata (AG) is mainly distributed in Chinese provinces and areas south of the Yangtze River Basin. It is mostly concentrated or scattered in mountainous bushes or woods with high humidity. Approximately 57 chemical components of AG have been identified, including flavonoids, phenols, steroids and terpenoids, volatile components, and other chemical components. In vitro studies have shown that the flavone of AG has therapeutic properties such as anti-bacteria, anti-inflammation, anti-oxidation, enhancing immunity, regulating glucose and lipid metabolism, being hepatoprotective, and being anti-tumor with no toxicity. Through searching and combing the related literature, this paper comprehensively and systematically summarizes the research progress of AG, including morphology, traditional and modern uses, chemical composition and structure, and pharmacological and toxicological effects, with a view to providing references for AG-related research.

The antifungal metabolites isolated from maize endophytic fungus Fusarium sp. induced by OSMAC strategy.

Six new sesquiterpenes, fusarchlamols A-F (1, 2, 4-7); one new natural product of sesquiterpenoid, methyltricinonoate (3); and ten known compounds were found from Fusarium sp. cultured in two different media by the one strain many compounds strategy. The compounds (1, 2, and 4-11) were isolated from Fusarium sp. in PDB medium, and compounds (3-5, 8, and 10-17) were discovered from Fusarium sp. in coffee medium. Additionally, the configuration of 8 was first reported in the research by Mosher's method. The structures were established by 1D, 2D NMR, mass spectrometry, calculated ECD spectra, and Mosher's method. Compounds 1, 2, 6/7, 12, and 16 indicated significant antifungal activities against the phytopathogen Alternaria alternata isolated from Coffea arabica with MICs of 1 µg/mL. The investigation on the anti-phytopathogen activity of metabolites can provide lead compounds for agrochemicals.

Effect of electroacupuncture intervention on the spinal cord PPIA/NF-κB signaling pathway in mice with amyotrophic lateral sclerosis. / ç”µé’ˆå¯¹è‚ŒèŽç¼©ä¾§ç´¢ç¡¬åŒ–ç—‡å°é¼ è„Šé«“PPIA/NF-κB信号通路的影响.

OBJECTIVES: To observe the effects of electroacupuncture (EA) on motor function, expression of extracellular cyclophile A(PPIA) and PPIA/nuclear factor-κB (NF-κB) signaling pathway in spinal cord of amyotrophic la-teral sclerosis (ALS) mice, so as to explore the mechanism of EA intervention in regulating extracellular PPIA on neuroinflammation in ALS mice. METHODS: Thirty ALS-SOD1G93A mice with hSOD1-G93A gene were randomly divided into model, EA and Riluzole groups , with 10 mice in each group, and other 10 ALS-SOD1G93A negative mice were used as the blank group. EA was applied to bilateral "Yanglingquan"(GB34) and "Zusanli"(ST36) for 20 min once daily, 5 days a week for 2 weeks. In the Riluzole group, riluzole solution (30 mg·kg-1·d-1) was administrated intragastrically, and the treatment time was the same as that in the EA group.Rotating rod experiment and open field experiment were used to evaluate the changes in motor function of mice .The morphology of motor neurons in the anterior horn of spinal cord was observed by HE staining.The relative protein expression levels of PPIA, TDP-43 and NF-κB in the spinal cord were detected by Western blot.The positive expression level of TDP-43 in the spinal cord was detected by immunohistochemistry. The positive expression level of PPIA in spinal cord was marked by immunofluorescence. Serum PPIA content was determined by ELISA. RESULTS: Compared with the blank group, the time of rod dropping and the total distance of open field movement in the model group were shortened (P<0.01), the number of motor neurons in the anterior horn of the spinal cord was reduced, the cell morphology was incomplete, the cell body was atrophied, the protein expression and positive expression of TDP-43 were increased (P<0.01), the protein expressions of PPIA and NF-κB in the spinal cord were increased(P<0.01), the serum content of PPIA and immunofluorescence expression of PPIA in spinal cord were increased (P<0.01). Compared with the model group, the time of rod dropping and the total distance of open field movement of mice in the EA group and the Riluzole group were prolonged (P<0.05, P<0.01), and the injury of motor neuron in the anterior horn of the spinal cord was decreased, the protein expression and positive expression of TDP-43 in the spinal cord were decreased (P<0.05, P<0.01)；the relative expression levels of PPIA and NF-κB proteins were decreased (P<0.05, P<0.01), and the content of PPIA in serum and the immunofluorescence expression of PPIA in the spinal cord were decreased (P<0.05, P<0.01) in the EA group；the relative protein expression of NF-κB and fluorescence expression of PPIA in spinal cord of mice in the Riluzole group were decreased (P<0.05). CONCLUSIONS: EA intervention can improve motor function in ALS mice, and its mechanism may be related to the inhibition of PPIA/NF-κB signaling pathway by EA to alleviating neuroinflammatory response.

Research progress on the molecular mechanism of electroacupuncture at "Zusanli" (ST36) for regulating gastrointestinal dysfunction. / 电针"足三里"è°ƒèŠ‚èƒƒè‚ åŠŸèƒ½å¼‚å¸¸çš„åˆ†å­æœºåˆ¶ç ”ç©¶è¿›å±•.

Gastrointestinal dysfunction is manifested as digestive symptoms. Clinically, Zusanli (ST36) is crucial in the acupoint prescriptions of acupuncture no matter which type of the disease is differentiated in traditional Chinese medicine, but the underlying mechanism remains to be explored. Aiming to summarize the current status of the researches in terms of ameliorating gastrointestinal mucosal damage and regulating gastrointestinal motility disorders, we systematically reviewed the basic researches on the intervention with electroacupuncture (EA) at "ST36" in treatment of the diseases related to gastrointestinal dysfunction in the past 5 years, after searching the articles from Chinese and English databases. The results suggest that EA at ST36 may regulate the local gastrointestinal inflammation, oxidative stress and immune microenvironment to relieve gastrointestinal mucosal damage and adjust gastrointestinal motility disorders by means of modulating the central and peripheral nerve signaling as well as the function of mast cells and Cajal interstitial cells.

UPLC-Q-TOF-MS based investigation into the bioactive compounds and molecular mechanisms of Lamiophlomis Herba against hepatic fibrosis.

BACKGROUND: Lamiophlomis Herba (LH) is a valuable traditional medicinal plant found on the Qinghai-Tibetan Plateau that promotes blood circulation, removes blood stasis, and has antibacterial and anti-inflammatory properties. The main components of LH are iridoid glycosides, phenethyl alcohol glycosides, flavonoids, and polysaccharides. PURPOSE: To investigate the mechanism of the anti-liver fibrosis effects of LH and screen for its bioactive compounds. STUDY DESIGN: Screening LH marker components and validating the LH anti-liver fibrosis mechanism. METHODS: The active ingredients of LH were identified using UPLC-Q-TOF-MS, and HotMap combined with principal components analysis (PCA) was used to screen for marker components. Network pharmacology and molecular docking techniques were used to predict the potential anti-fibrotic targets of LH. Immunofluorescence, enzyme-linked immunosorbent assay (ELISA), real-time PCR (RT-PCR), and western blotting were used for experimental validation and mechanistic studies. RESULTS: Fifteen compounds that actively contributed to the cluster were identified as marker compounds. Acteoside, 8-O-acetyl shanzhiside methyl ester (8-O-ASME), Luteolin, Shanzhiside Methyl ester (SME), Loganin, Loganate were the main active components. Network pharmacology and molecular docking studies have shown that LH might improve liver fibrosis, inflammation, and oxidative stress, which might be related to key targets such as PTGS2, MAPK, EGFR, AKT1, SRC, Fn1, Col3a1, Col1a1, and PC-III. The results of ELISA, RT-PCR and western blot experiments showed that Acteoside, 8-O-ASME, Luteolin, SME, Loganin, Loganate, and the LH group could reduce the levels of fibronectin, Col1a1, Col3a1, α-SMA, Col-Ⅳ, LN, and PC-Ⅲ. CONCLUSION: LH improves liver fibrosis induced by HSC-T6 cells and inhibits the deposition of extracellular matrix (ECM) in hepatocytes, resulting in a decrease in the degree of liver fibrosis and a good anti-liver fibrosis effect.

Efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition-associated hyperglycemia: a systematic review and network meta-analysis.

Aims: To systematically evaluate the efficacy and safety of different insulin infusion methods in the treatment of total parenteral nutrition (TPN)-associated hyperglycemia based on published literature and the data of completed clinical trials using a network meta-analysis. Methods: A comprehensive search of PubMed, Elsevier, Web of Science, EMBASE, Medline, clinicaltrials.gov, Cochrane Library, and three Chinese databases (Wanfang Data, China National Knowledge Infrastructure, and SINOMED) up to December 15, 2022, was performed to collect information on different insulin infusion methods used for the treatment of TPN-associated hyperglycemia, and the Cochrane systematic review method was used to screen the literature, evaluate the quality of the included literature, and extract clinical characteristics for a network meta-analysis. Clinical outcomes included mean blood glucose (MBG), hypoglycemia, hospital length of stay, hyperglycemia, surgical site infection (SSI) and mean total daily insulin. Results: A total of 21 articles, including 1,459 patients, were included to analyze 6 different routes of insulin infusion, including continuous intravenous insulin infusion (CVII), continuous subcutaneous insulin infusion (CSII), subcutaneous glargine insulin (s.c. GI), the addition of regular insulin to the PN mixture (RI-in-PN), multiple subcutaneous insulin injections (MSII) and 50% of insulin administered as RI-in-PN + 50% of insulin administered as s.c. GI (50% RI-in-PN + 50% s.c. GI). The results of the network meta-analysis showed that MSII was the least effective in terms of MBG, followed by CVII. The 6 interventions were basically equivalent in terms of the hypoglycemia incidence. In terms of the length of hospital stay, patients in the CVII group had the shortest hospital stay, while the MSII group had the longest. CVII was the best intervention in reducing the incidence of hyperglycemia. The incidence of SSI was the lowest in the CSII and CVII groups, and the mean daily insulin dosage was the lowest in the CVII group. Conclusion: Current literature shows that for the treatment of TPN-associated hyperglycemia, CVII is the most effective, reducing the incidence of hyperglycemia and shortening the length of hospital stay without increasing the incidence of hypoglycemia. MSII has the worst efficacy, leading to a higher MBG and longer hospital stay, and RI-in-PN, CSII, s.c. GI and 50% RI-in-PN + 50% s.c. GI are better in terms of efficacy and safety and can be substituted for each other. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023439290.

A Missense Variant in AIFM1 Caused Mitochondrial Dysfunction and Intolerance to Riboflavin Deficiency.

AIFM1 is a mitochondrial flavoprotein involved in caspase-independent cell death and regulation of respiratory chain complex biogenesis. Mutations in the AIFM1 gene have been associated with multiple clinical phenotypes, but the effectiveness of riboflavin treatment remains controversial. Furthermore, few studies explored the reasons underlying this controversy. We reported a 7-year-old boy with ataxia, sensorimotor neuropathy and muscle weakness. Genetic and histopathological analyses were conducted, along with assessments of mitochondrial function and apoptosis level induced by staurosporine. Riboflavin deficiency and supplementation experiments were performed using fibroblasts. A missense c.1019T > C (p. Met340Thr) variant of AIFM1 was detected in the proband, which caused reduced expression of AIFM1 protein and mitochondrial dysfunction as evidenced by downregulation of mitochondrial complex subunits, respiratory deficiency and collapse of ΔΨm. The proportion of apoptotic cells in mutant fibroblasts was lower than controls after induction of apoptosis. Riboflavin deficiency resulted in decreased AIFM1 protein levels, while supplementation with high concentrations of riboflavin partially increased AIFM1 protein levels in variant fibroblasts. In addition, mitochondrial respiratory function of mutant fibroblasts was partly improved after riboflavin supplementation. Our study elucidated the pathogenicity of the AIFM1 c.1019T > C variant and revealed mutant fibroblasts was intolerant to riboflavin deficiency. Riboflavin supplementation is helpful in maintaining the level of AIFM1 protein and mitochondrial respiratory function. Early riboflavin treatment may serve as a valuable attempt for patients with AIFM1 variant.

Epinodosin suppresses the proliferation, invasion, and migration of esophageal squamous cell carcinoma by mediating miRNA-143-3p/Bcl-2 axis.

Epinodosin has shown antibacterial and antitumor biological characteristics in the documents. We found that Epinodosin has an effective inhibitory effect on esophageal squamous cell carcinoma (ESCC). However, the potential roles and mechanisms of Epinodosin in ESCC remain unclear. We performed many experiments to clarify the effect and mechanism of Epinodosin on ESCC. In this study, cell viability, invasion, migration, and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,-diphenytetrazoliumromide (MTT), Transwell, and flow cytometry. The differentially expressed miRNAs were screened through RNA transcriptome sequencing. The expression levels of miRNA-143-3p and some proteins were measured by real-time polymerase chain reaction (PCR) and Western blot. The anticancer effects of Epinodosin in vivo were determined by a nude mouse model. Epinodosin suppressed cell proliferation/invasion/migration and induced ESCC cell apoptosis. Epinodosin remarkably affected the protein expression of mitogen-activated protein kinase (MAPK) signaling pathway. The animal experiments demonstrated that Epinodosin could attenuate the growth of ESCC tumors in nude mice. The expression of p53, Bim, and Bax was upregulated, while that of Bcl-2 was downregulated in tumor tissues. In conclusion, Epinodosin suppresses cell viability/invasion/migration, while induces ESCC cell apoptosis by mediating miRNA-143-3p and Bcl-2, and can markedly attenuate the growth of ESCC tumors in nude mice.

An Externally Validated Nomogram for Predicting the Overall Survival of Patients With Diffuse Large B-Cell Lymphoma Based on Clinical Characteristics and Systemic Inflammatory Markers.

Background: Systemic inflammatory indicators are clinically significant in guiding diffuse large B-cell lymphoma (DLBCL) prognosis. However, which inflammatory markers are the best predictors of DLBCL prognosis is still unclear. In this study, we aimed to create a nomogram based on the best inflammatory markers and clinical indicators to predict the overall survival of patients with DLBCL. Patients and methods: We analyzed data from 423 DLBCL patients from two institutions and divided them into a training set, an internal validation set, and an external validation set (n = 228, 97, and 98, respectively). The least absolute shrinkage and selection operator and Cox regression analysis were used to develop nomograms. We assessed model fit using the Akaike information criterion and Bayesian information criterion. The concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram's predictive performance and clinical net benefit and compared with the International Prognostic Index (IPI) and National Comprehensive Cancer Network (NCCN)-IPI. Results: The inclusion variables for the nomogram model were age, Eastern Cooperative Oncology Group performance status, lactate dehydrogenase level, the systemic immune-inflammation index (SII), the prognostic nutritional index (PNI), and ß-2 microglobulin (ß-2 MG) level. In the training cohort, the nomogram showed better goodness of fit than the IPI and NCCN-IPI. The C-index of the nomogram (0.804, 95% CI: 0.751-0.857) outperformed the IPI (0.690, 95% CI: 0.629-0.751) and NCCN-IPI (0.691, 95% CI: 0.632-0.750). The calibration curve, ROC curve, and DCA curve analysis showed that the nomogram has satisfactory predictive power and clinical utility. Similar results were found in the validation cohort. Conclusion: The nomogram integrated with the clinical characteristics and inflammatory markers is beneficial to predict the prognosis of patients with DLBCL.