Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-ß1/Smad3 pathways.

Background: Sepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1ß/Smad3 pathways. Methods: A septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. Results: DCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-ß1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. Conclusions: DCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.

Advancements in the Study of Biologic Agents in Comorbidities of Psoriasis: A Literature Review.

This literature review systematically searched relevant literature from the past 10 years using various medical databases, including PubMed, Medline, Cochrane, China National Knowledge Infrastructure (CNKI), Wanfang, and Weipu. As a chronic inflammatory disease, psoriasis is associated with various cells and cytokines of the body's immune system, making them more susceptible to various systemic comorbidities than the general population. At a time when conventional regimens are ineffective and there is a lack of personalized treatment options for such comorbidities, the development of biologics has revolutionized the treatment of psoriasis comorbidities, and a number of biologic combination therapies have been incorporated into first-line treatments in many countries. The focus of this review was to investigate the relationship between psoriasis and comorbidities, such as metabolic syndrome, psoriatic arthritis, cardiovascular diseases, mental disorders, infectious diseases, digestive system diseases, and renal diseases. Furthermore, the study explored the significance of biologic therapies in the management of these comorbidities. Also this paper suggests current conditions and precautions for the use of biologic therapies to minimize the occurrence of adverse effects. This review was performed to provide guidance for clinical drug selection in patients with psoriasis and comorbidities, as well as serve as a reference for the development and application of biologic therapies.

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Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.

The regulatory effect of specialized pro-resolving mediators on immune cells.

Appropriate inflammation is an effective weapon for the body to fight against harmful stimuli, while excessive or prolonged inflammatory reactions could lead to tissue destruction, fibrosis, and even organ failure. The timely termination of inflammatory response is of great significance for maintaining the homeostasis of the body. Unlike the past perception that the regression of inflammation is a passive process, it is now considered that the regression of inflammation is a carefully coordinated active process. Specialized pro-resolving mediators (SPMs) play an important role in limiting the inflammatory response, promoting the regression of inflammation, and maintaining homeostasis. Increasing evidence suggests that exogenous treatment with SPMs could effectively improve symptoms in various inflammatory-related diseases. In this review, we briefly address the current family members of SPMs. We elaborated on the extensive regulation of SPMs of multiple immune cells in various inflammatory-related diseases and the related mechanisms. Our research provides a theoretical basis for promoting an understanding of the role and mechanism of SMPs in inflammation.

LINC00518 Promotes Cell Malignant Behaviors via Influencing EIF4A3-Mediated mRNA Stability of MITF in Melanoma.

Melanoma has become the most severe sort of skin cancer, deriving from the pigment-producing melanocytes. Existing research has validated that long noncoding RNAs (lncRNAs) have critical function in the progression of cancers. LINC00518 has been studied in cutaneous melanoma; however, the molecular mechanism of LINC00518 in melanoma needs in-depth investigation. In our study, LINC00518 was revealed to be upregulated in melanoma tissues and cells, and melanoma patients in high LINC00518 expression group had poorer prognosis as depicted in GEPIA database. Functional assays revealed that LINC00518 depletion inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, MITF was confirmed to be upregulated in melanoma tissues and cells, and melanoma patients in high MITF expression group had poorer prognosis as displayed in GEPIA database. MITF expression was positively connected to LINC00518 expression. Additionally, results of mechanism assays uncovered EIF4A3 could bind with LINC00518 and MITF, and LINC00518 recruited EIF4A3 to stabilize MITF mRNA. Finally, it was demonstrated that upregulation of MITF could partially abrogate the inhibitory impact of LINC00518 knockdown on melanoma cell malignant behaviors. To summarize, LINC00518 promotes the malignant processes of melanoma cells through targeting EIF4A3/MITF axis, which might provide novel potential biomarkers for melanoma prognosis.

Emodin Attenuates LPS-Induced Acute Lung Injury by Inhibiting NLRP3 Inflammasome-Dependent Pyroptosis Signaling Pathway In vitro and In vivo.

Emodin, the effective component of the traditional Chinese medicine Dahuang, has anti-inflammatory effects. However, the protective effects and potential mechanisms of emodin are not clear. This study investigated the protective effects and potential mechanisms of emodin on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in vitro and in vivo. In vivo, we designed an LPS-induced ALI rat model. In vitro, we chose the J774A.1 cell line to establish an inflammatory cellular model, and knocked down NOD-like receptor family pyrin domain containing 3 (NLRP3) using small interfering RNA. The mRNA and protein expression of NLRP3, a C-terminal caspase recruitment domain (ASC), caspase 1 (CASP1), and gasdermin D (GSDMD) in cells and lung tissues were detected by western blot and real-time quantitative polymerase chain reaction (PCR). The expression levels of interleukin 1 beta (IL-1ß) and IL-18 in the serum and supernatant were determined by the enzyme-linked immunosorbent assay. The degree of pathological injury in lung tissue was evaluated by hematoxylin and eosin (H&E) staining. In vitro, we demonstrated that emodin could inhibit NLRP3 and then inhibit the expression of ASC, CASP1, GSDMD, IL-1ß, and IL-18. In vivo, we confirmed that emodin had protective effects on LPS-induced ALI and inhibitory effects on NLRP3 inflammasome -dependent pyroptosis. Emodin showed excellent protective effects against LPS-induced ALI by regulating the NLRP3 inflammasome-dependent pyroptosis signaling pathway.

Assessment of Sequelae of COVID-19 Nearly 1 Year After Diagnosis.

Background: A previous study has shown that 81% of the COVID-19 patients had mild or moderate symptoms. However, most studies on the sequelae in COVID-19 patients focused on severe cases and the long-term follow-up studies on the health consequences in non-severe cases are limited. The current study aimed to assess the sequelae of COVID-19 in patients nearly 1 year after diagnosis with a particular focus on the recovery of patients with non-severe COVID-19. Methods: We enrolled 120 patients infected with SARS-CoV-2 discharged from Wuhan Union hospital west district (designated hospital for COVID-19) and Fangcang shelter hospitals between January 29, 2020 and April 1, 2020. All participants were asked to complete a series of questionnaires to assess their symptoms and quality of life and for psychological evaluation. Also, pulmonary function test, chest CT, 6-min walking test (6MWT), routine blood test, liver and kidney function tests, fasting blood glucose test, lipid test, and immunoglobulin G antibody test were performed to evaluate their health. Results: The mean age of the study population was 51.6 ± 10.8 years. Of the 120 patients, 104 (86.7%) were cases of non-severe COVID-19. The follow-up study was performed between November 23, 2020 and January 11, 2021, and the median time between the diagnosis and the follow-up was 314.5 (IQR, 296-338) days. Sleep difficulties, shortness of breath, fatigue, and joint pain were common symptoms observed during follow-up and nearly one-third of the non-severe cases had these symptoms. A total of 50 (41.7%) and 45 (37.5%) patients reported anxiety and depression, respectively. And 18.3% of the patients showed negative results in the IgG test at the follow-up, which correlated with the severity of the infection (R = 0.203, p = 0.026), and the proportion of IgG negative cases in non-severe COVID-19 patients was higher than that in the severe cases (20.2 vs. 6.3%). Pulmonary diffusion impairment was reported in 30 (26.1%) out of 115 patients, and 24 (24.2%) out of the 99 non-severe cases. The values of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FVC/FEV1, vital capacity (VC), total lung capacity (TLC), and residual volume (RV) were less than the normal range in 1.7, 8.6, 0.9, 11.2, 7.0, and 0.9% of the patients, respectively. A total of 55 (56.7%) out of the 97 patients showed abnormal CT findings, including ground-glass opacities (GGO), bronchiectasis, nodules, lines and bands, and fibrosis. Furthermore, there was a correlation between all the SF-36-domain scores and the duration of hospitalization, pulmonary function, and a 6MWT. Conclusions: At the nearly 1-year follow-up, COVID-19 survivors still had multi-system issues, including those in the respiratory functioning, radiography, quality of life, and anxiety and depression. Moreover, non-severe cases also showed some sequelae and the proportion of IgG negative cases in the non-severe patients was higher than that in severe cases. Therefore, conducting follow-ups and preventing the reinfection of SARS-CoV-2 in this group is necessary.

EMT-associated microRNAs and their roles in cancer stemness and drug resistance.

Epithelial-to-mesenchymal transition (EMT) is implicated in a wide array of malignant behaviors of cancers, including proliferation, invasion, and metastasis. Most notably, previou studies have indicated that both cancer stem-like properties and drug resistance were associated with EMT. Furthermore, microRNAs (miRNAs) play a pivotal role in the regulation of EMT phenotype, as a result, some miRNAs impact cancer stemness and drug resistance. Therefore, understanding the relationship between EMT-associated miRNAs and cancer stemness/drug resistance is beneficial to both basic research and clinical treatment. In this review, we preliminarily looked into the various roles that the EMT-associated miRNAs play in the stem-like nature of malignant cells. Then, we reviewed the interaction between EMT-associated miRNAs and the drug-resistant complex signaling pathways of multiple cancers including lung cancer, gastric cancer, gynecologic cancer, breast cancer, liver cancer, colorectal cancer, pancreatic cancer, esophageal cancer, and nasopharyngeal cancer. We finally discussed the relationship between EMT, cancer stemness, and drug resistance, as well as looked forward to the potential applications of miRNA therapy for malignant tumors.

Emodin Protects Sepsis Associated Damage to the Intestinal Mucosal Barrier Through the VDR/ Nrf2 /HO-1 Pathway.

Aims: Emodin is an anthraquinone extracted from Polygonum multiflorum, which has potential anti-inflammatory and anti-oxidative stress effects. However, the possible protective mechanism of emodin is unclear. The purpose of this study was to investigate the protective mechanism of emodin against cecal ligation and puncture and LPS-induced intestinal mucosal barrier injury through the VDR/ Nrf2 /HO-1 signaling pathway. Methods: We established a mouse model of sepsis by cecal ligation and puncture (CLP), and stimulated normal intestinal epithelial cells with lipopolysaccharide (LPS). VDR in cellswas down-regulated by small interfering ribonucleic acid (siRNA) technology.Mice were perfused with VDR antagonists ZK168281 to reduce VDR expression and mRNA and protein levels of VDR and downstream molecules were detected in cells and tissue. Inflammation markers (tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6)) and oxidative stress markers (superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH)) were measured in serum and intestinal tissueby enzym-linked immunosorbent assay. The expression of VDR in intestinal tissue was detected by immunofluorescence. Histopathological changes were assessed by hematoxylin and eosin staining. Results: In NCM460 cells and animal models, emodin increased mRNA and protein expression of VDR and its downstream molecules. In addition, emodin could inhibit the expressions of TNF-α, IL-6 and MDA in serum and tissue, and increase the levels of SOD and GSH. The protective effect of emodin was confirmed in NCM460 cells and mice, where VDR was suppressed. In addition, emodin could alleviate the histopathological damage of intestinal mucosal barrier caused by cecal ligation and puncture. Conclusion: Emodin has a good protective effect against sepsis related intestinal mucosal barrier injury, possibly through the VDR/ Nrf2 /HO-1 pathway.

HDAC3 deteriorates colorectal cancer progression via microRNA-296-3p/TGIF1/TGFß axis.

BACKGROUND: The mechanism of histone deacetylase 3 (HDAC3) in colorectal cancer (CRC) has already been discussed. However, the feedback loop of HDAC3/microRNA (miR)-296-3p and transforming growth factor ß-induced factor 1 (TGIF1) in CRC has not been explained clearly. Thus, the mainstay of this study is to delve out the mechanism of this axis in CRC. METHODS: To demonstrate that HDAC3 regulates the miR-296-3p/TGIF1/TGFß axis and is involved in CRC progression, a series of cell biological, molecular and biochemical approaches were conducted from the clinical research level, in vitro experiments and in vivo experiments. These methods included RT-qPCR, Western blot assay, cell transfection, MTT assay, EdU assay, flow cytometry, scratch test, Transwell assay, dual luciferase reporter gene assay, chromatin immunoprecipitation, nude mouse xenograft, H&E staining and TUNEL staining. RESULTS: Higher HDAC3 and TGIF1 and lower miR-296-3p expression levels were found in CRC tissues. HDAC3 was negatively connected with miR-296-3p while positively correlated with TGIF1, and miR-296-3p was negatively connected with TGIF1. Depleted HDAC3 elevated miR-296-3p expression and reduced TGIF1 expression, decreased TGFß pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by miR-296-3p knockdown. Restored miR-296-3p suppressed TGIF1 and reduced TGFß pathway-related proteins, inhibited CRC proliferation, invasion, and migration in vitro and slowed down tumor growth and induction of apoptosis in vivo, which were reversed by TGIF1 overexpression. CONCLUSION: This study illustrates that down-regulation of HDAC3 or TGIF1 or up-regulation of miR-296-3p discourages CRC cell progression and slows down tumor growth, which guides towards a novel direction of CRC treatment.