Bergamot essential oil improves CUMS-induced depression-like behaviour in rats by protecting the plasticity of hippocampal neurons.

Bergamot essential oil (BEO) is an extract of the bergamot fruit with significant neuroprotective effect. This study was to investigate the effects and the underlying mechanism of BEO in mitigating depression. GC-MS were used to identify its constituents. Antidepressive properties of BEO were evaluated by sucrose preference test (SPT), force swimming test (FST) and open field test (OFT). Nissl staining was used to determine the number of Nissl bodies in hippocampus (HIPP) of rats. Changes in HIPP dendritic length and dendritic spine density were detected by Golgi-Cox staining. Immunohistochemistry and Western blot were used to detect the postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP) in the HIPP of rats. The enzyme-linked immunosorbent assay was used to determine the 5-hydroxytryptamine (5-HT), insulin-like growth factor 1 (IGF-1) and interleukin-1ß (IL-1ß) in the HIPP, serum and cerebrospinal fluid (CSF) of rats. Inhaled BEO significantly improved depressive behaviour in chronic unpredictable mild stress (CUMS) rats. BEO increased Nissl bodies, dendritic length and spine density, PSD-95 and SYP protein in the HIPP. Additionally, BEO upregulated serum 5-HT, serum and CSF IGF-1, while downregulating serum IL-1ß. Collectively, inhaled BEO mitigates depression by protecting the plasticity of hippocampal neurons, hence, providing novel insights into treatment of depression.

An novel effective and safe model for the diagnosis of nonalcoholic fatty liver disease in China: gene excavations, clinical validations, and mechanism elucidation.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. NAFLD leads to liver fibrosis and hepatocellular carcinoma, and it also has systemic effects associated with metabolic diseases, cardiovascular diseases, chronic kidney disease, and malignant tumors. Therefore, it is important to diagnose NAFLD early to prevent these adverse effects. METHODS: The GSE89632 dataset was downloaded from the Gene Expression Omnibus database, and then the optimal genes were screened from the data cohort using lasso and Support Vector Machine Recursive Feature Elimination (SVM-RFE). The ROC values of the optimal genes for the diagnosis of NAFLD were calculated. The relationship between optimal genes and immune cells was determined using the DECONVOLUTION algorithm CIBERSORT. Finally, the specificity and sensitivity of the diagnostic genes were verified by detecting the expression of the diagnostic genes in blood samples from 320 NAFLD patients and liver samples from 12 mice. RESULTS: Through machine learning we identified FOSB, GPAT3, RGCC and RNF43 were the key diagnostic genes for NAFLD, and they were further demonstrated by a receiver operating characteristic curve analysis. We found that the combined diagnosis of the four genes identified NAFLD samples well from normal samples (AUC = 0.997). FOSB, GPAT3, RGCC and RNF43 were strongly associated with immune cell infiltration. We also experimentally examined the expression of these genes in NAFLD patients and NAFLD mice, and the results showed that these genes are highly specific and sensitive. CONCLUSIONS: Data from both clinical and animal studies demonstrate the high sensitivity, specificity and safety of FOSB, GPAT3, RGCC and RNF43 for the diagnosis of NAFLD. The relationship between diagnostic key genes and immune cell infiltration may help to understand the development of NAFLD. The study was reviewed and approved by Ethics Committee of Tianjin Second People's Hospital in 2021 (ChiCTR1900024415).

The dynamic shifts of IL-10-producing Th17 and IL-17-producing Treg in health and disease: a crosstalk between ancient "Yin-Yang" theory and modern immunology.

The changes in T regulatory cell (Treg) and T helper cell (Th) 17 ratios holds paramount importance in ensuring internal homeostasis and disease progression. Recently, novel subsets of Treg and Th17, namely IL-17-producing Treg and IL-10-producing Th17 have been identified. IL-17-producing Treg and IL-10-producing Th17 are widely considered as the intermediates during Treg/Th17 transformation. These "bi-functional" cells exhibit plasticity and have been demonstrated with important roles in multiple physiological functions and disease processes. Yin and Yang represent opposing aspects of phenomena according to the ancient Chinese philosophy "Yin-Yang" theory. Furthermore, Yin can transform into Yang, and vice versa, under specific conditions. This theory has been widely used to describe the contrasting functions of immune cells and molecules. Therefore, immune-activating populations (Th17, M1 macrophage, etc.) and immune overreaction (inflammation, autoimmunity) can be considered Yang, while immunosuppressive populations (Treg, M2 macrophage, etc.) and immunosuppression (tumor, immunodeficiency) can be considered Yin. However, another important connotation of "Yin-Yang" theory, the conversion between Yin and Yang, has been rarely documented in immune studies. The discovery of IL-17-producing Treg and IL-10-producing Th17 enriches the meaning of "Yin-Yang" theory and further promotes the relationship between ancient "Yin-Yang" theory and modern immunology. Besides, illustrating the functions of IL-17-producing Treg and IL-10-producing Th17 and mechanisms governing their differentiation provides valuable insights into the mechanisms underlying the dynamically changing statement of immune statement in health and diseases.

Bazi Bushen alleviates skin senescence by orchestrating skin homeostasis in SAMP6 mice.

Bazi Bushen, a Chinese-patented drug with the function of relieving fatigue and delaying ageing, has been proven effective for extenuating skin senescence. To investigate the potential mechanism, senescence-accelerated mouse prone 6 (SAMP6) was intragastrically administered with Bazi Bushen for 9 weeks to induce skin homeostasis. Skin homeostasis is important in mitigating skin senescence, and it is related to many factors such as oxidative stress, SASP, apoptosis, autophagy and stem cell. In our study, skin damage in SAMP6 mice was observed using HE, Masson and SA-ß-gal staining. The content of hydroxyproline and the activities of SOD, MDA, GSH-PX and T-AOC in the skin were measured using commercial assay kits. The level of SASP factors (IL-6, IL-1ß, TNF-α, MMP2 and MMP9) in skin were measured using ELISA kits. The protein expressions of p16, p21, p53, Bax, Bcl-2, Cleaved caspase-3, LC3, p62, Beclin1, OCT4, SOX2 and NANOG were measured by western blotting. The expression of ITGA6 and COL17A1 was measured by immunofluorescence staining and western blotting. Our findings demonstrated that Bazi Bushen alleviated skin senescence by orchestrating skin homeostasis, reducing the level of oxidative stress and the expression of SASP, regulating the balance of apoptosis and autophagy and enhancing the protein expressions of ITGA6 and COL17A1 to improve skin structure in SAMP6 mice. This study indicated that Bazi Bushen could serve as a potential therapy for alleviating skin senescence.

Bazi Bushen maintains intestinal homeostasis through inhibiting TLR4/NFκB signaling pathway and regulating gut microbiota in SAMP6 mice.

BACKGROUND: Bazi Bushen is a Chinese patented medicine with multiple health benefits and geroprotective effects, yet, no research has explored its effects on intestinal homeostasis. In this study, we aimed to investigate the effect of Bazi Bushen on intestinal inflammation and the potential mechanism of gut microbiota dysbiosis and intestinal homeostasis in senescence-accelerated mouse prone 6 (SAMP6). The hematoxylin and eosin (H&E) staining and immunohistochemistry were performed to assess the function of the intestinal mucosal barrier. The enzyme-linked immunosorbent assay (ELISA) and Western blotting were used to determine the level of intestinal inflammation. The aging-related ß-galactosidase (SA-ß-gal) staining and Western blotting were used to measure the extent of intestinal aging. The 16S ribosomal RNA (16S rRNA) was performed to analyze the change in gut microbiota composition and distribution. RESULTS: Bazi Bushen exerted remarkable protective effects in SAMP6, showing a regulated mucosal barrier and increased barrier integrity. It also suppressed intestinal inflammation through down-regulating pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) and inhibiting TLR4/NFκB signaling pathway (MYD88, p-p65, and TLR4). Bazi Bushen improved intestinal aging by reducing the area of SA-ß-gal-positive cells and the expression of senescence markers p16, p21, and p53. In addition, Bazi Bushen effectively rebuilt the gut microbiota ecosystem by decreasing the abundance of Bacteroides and Klebsiella, whiles increasing the ratio of Lactobacillus/Bacteroides and the abundance of Akkermansia. CONCLUSION: Our study shows that Bazi Bushen could serve as a potential therapy for maintaining intestinal homeostasis. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Effect of Jiangan-Jiangzhi Pill on Gut Microbiota and Chronic Inflammatory Response in Rats with Non-Alcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease with high rates of occurrence. Research has found that NAFLD patients experience varying degrees of intestinal flora imbalance. There is evidence that traditional Chinese medicine (TCM) positively regulates imbalances in the gut microbiota caused by liver diseases. Jiangan-Jiangzhi pill (JGJZ) is a common Chinese remedy that can treat NAFLD clinically. This article investigates how JGJZ affects NAFLD and assesses related changes in the intestinal flora. We established a NAFLD rat model by feeding them a high-fat diet (HFD) and gave different interventions. After twelve weeks, the results revealed that JGJZ decreased the total cholesterol, triglyceride, alanine aminotransferase, and aspartate aminotransferase in the serum of NAFLD rats. Histopathological staining demonstrated that JGJZ relieved cellular fat accumulation in the liver. Inflammatory cytokine levels (IL-6, IL-1ß, and TNF-α) were down-regulated. Analysis of 16S rRNA demonstrated that JGJZ changed the community compositional structure of gut microbiota, characterized by a decrease in the Firmicutes-to-Bacteroidetes ratio, and increased gut microbiota diversity and the abundance of dominant groups. Accordingly, our study illustrated that JGJZ exerted a better effect in treating HFD-induced NAFLD, which may be closely related to ameliorating gut microbiota dysbiosis.

Effect of fecal microbiota transplantation in patients with slow transit constipation and the relative mechanisms based on the protein digestion and absorption pathway.

BACKGROUND: Fecal microbiota transplantation (FMT) is considered an effective treatment for slow transit constipation (STC); nevertheless, the mechanism remains unclear. METHODS: In this study, eight patients with STC were selected according to the inclusion and exclusion criteria; they then received three treatments of FMT. The feces and serum of STC patients were collected after each treatment and analyzed by integrating 16 s rRNA microbiome and metabolomic analyses. RESULTS: The results showed that the percentage of clinical improvement reached 62.5% and the rates of patients' clinical remission achieved 75% after the third treatment. At the same time, FMT improved the Wexner constipation scale (WCS), the Gastrointestinal Quality-of-Life Index (GIQLI) and Hamilton Depression Scale (HAMD). Fecal microbiome alpha diversity and beta diversity altered significantly after FMT. Analysis of the 16 s rRNA microbiome showed that the numbers of Bacteroidetes (Prevotell/Bacteroides) and Firmicute (Roseburia/Blautia) decreased, whereas Actinobacteria (Bifidobacterium), Proteobacteria (Escherichia), and Firmicute (Lactobacillus) increased after FMT. The metabolomics analyses showed that the stool of FMT-treated patients were characterized by relatively high levels of N-Acetyl-L-glutamate, gamma-L-glutamyl-L-glutamic acid, Glycerophosphocholine, et al., after FMT. Compared with baseline, the serum of treated patients was characterized by relatively high levels of L-Arginine, L-Threonine, Ser-Arg, Indoleacrylic acid, Phe-Tyr, 5-L-Glutamyl-L-alanine, and lower levels of Erucamide after the treatment. The correlation analysis between the metabolites and gut microbiota showed a significant correlation. For example, L-Arginine was positively correlated with lactobacillus, et al. L-Threonine was positively correlated with Anaerovibrio, Sediminibacterium but negatively correlated with Phascolarctobacterium. Erucamide had significant negative correlations with Sediminibacterium and Sharpea, while being positively correlated with Phascolarctobacterium. Enriched KEGG pathways analysis demonstrated that the protein digestion and absorption pathways gradually upregulated with the increase of FMT frequency. The L-Arginine and L-Threonine were also involved in the pathway. A large amount of Na + was absorbed in the pathway, so that it might increase mucus secretion and electrical excitability of GI smooth muscle. CONCLUSIONS: Therefore, we speculated that FMT changed the patients' gut microbiota and metabolites involved in the protein digestion and absorption pathways, thereby improving the symptoms of STC. Study on the effectiveness and safety of FMT in the treatment of STC. The study was reviewed and approved by Ethics Committee of Tianjin People's Hospital (ChiCTR2000033227) in 2020.

Transcriptome and complete chloroplast genome of Glycyrrhiza inflata and comparative analyses with the other two licorice species.

In this study, we characterized the transcriptome and chloroplast genome of Glycyrrhiza inflata and performed comparative analyses with G. uralensis and G. glabra. 60,541unigenes were obtained from the transcriptome of G. inflata. The results of function annotation revealed a similar distribution of functional categories among three licorice species. By comparing chloroplast genomes of licorice species, it was demonstrated that the structure and the length of genome as well as gene content and gene order were highly similar. The phylogenetic tree, constructed with the mixed data of transcriptome and chloroplast genome, elucidated that G. inflata and G. glabra had a closer relationship than G. uralensis. Six regions were suggested as potential markers for the identification of three licorice species. In each licorice species, two unigenes were homologous to reference flavonol synthase. For G. inflata, 48 and 21 RNA editing sites were detected by PREP-Cp program and RNA-Seq data mapping, respectively.

The effects of a hirudin/liposome complex on a diabetic nephropathy rat model.

BACKGROUND: Hirudin, an extract from Hirudo spp., is an anticoagulant used to treat a variety of renal diseases, including diabetic nephropathy (DN). Currently, hirudin has to be used at high dosages to treat DN because it poorly targets the kidneys, although at high dosages it can have severe side effects. Developing a targeted drug delivery system for hirudin, then, could boost its positive therapeutic effects while lowering the risk of side effects. Liposomes have been demonstrated to have significant renal targeting potential, but here we show that a hirudin-loaded liposome is an effective delivery method for patients with DN. METHOD: In this study, we prepared a hirudin/liposome complex and tested its efficacy by injecting it into a rat model. We then compared the renal accumulation of hirudin between complex-injected rat models and rat models that received injections of hirudin alone. We also investigated the mechanisms behind the complex's effects. RESULT: The hirudin/liposome complex increased the accumulation of hirudin in kidney tissues and relieved the renal injury in DN rat models. Moreover, the hirudin/liposome complex down-regulated the expression of TGF-ß1 and VEGF in the kidneys. CONCLUSION: We demonstrated that a hirudin/liposome complex can have a significant positive effect on DN. The mechanism may be that the complex inhibits the expression of VEGF and TGF-ß1.

Inhibition effect of glycyrrhiza polysaccharide (GCP) on tumor growth through regulation of the gut microbiota composition.

Glycyrrhiza Uralensis Polysaccharide (GCP), as a macromolecular polysaccharide extracted from the Traditional Chinese Medicine (TCM) - Licorice has been proved to inhibit tumor growth in vitro and in vivo; however, the specific anti-tumor mechanism of GCP needs to be further investigated. In this study, we explore the anti-tumor mechanism of GCP from the angle of gut microbiota. Colon carcinoma cells (CT-26) were used to set up a tumor-bearing mouse model. After 14 days of GCP treatment, the weights of tumors were significantly reduced. In addition, HE staining of tissue sections reflected that GCP could effectively inhibit tumor metastasis. 16SrRNA high-throughput sequencing of fecal samples showed a significant change between the model group and GCP group in the composition of gut microbiota. Subsequently, gut microbiota depletion and fecal transplantation experiments further confirmed the relationship between the anti-tumor effects of GCP and gut microbiota. Following depletion of gut microbiota, GCP cannot inhibit tumor growth. Fecal transplantation experiments found that transplanting the feces of GCP-treated mice, to a certain extent, could inhibit tumor growth and metastasis. These results indicate that Glycyrrhiza Polysaccharides exert anti-tumor effects by affecting gut microbiota composition.

Icariin combined with human umbilical cord mesenchymal stem cells significantly improve the impaired kidney function in chronic renal failure.

At present, the main therapy for chronic renal failure (CRF) is dialysis and renal transplantation, but neither obtains satisfactory results. Human umbilical cord mesenchymal stem cells (huMSCs) are isolated from the fetal umbilical cord which has a high self-renewal and multi-directional differentiation potential. Icariin (ICA), a kidney-tonifying Chinese Medicine can enhance the multipotency of huMSCs. Therefore, this work seeks to employ the use of ICA-treated huMSCs for the treatment of chronic renal failure. Blood urea nitrogen and creatinine (Cr) analyses showed amelioration of functional parameters in ICA-treated huMSCs for the treatment of CRF rats at 3, 7, and 14 days after transplantation. ICA-treated huMSCs can obviously increase the number of cells in injured renal tissues at 3, 7, and 14 days after transplantation by optical molecular imaging system. Hematoxylin-eosin staining demonstrated that ICA-treated huMSCs reduced the levels of fibrosis in CRF rats at 14 days after transplantation. Superoxide dismutase and Malondialdehyde analyses showed that ICA-treated huMSCs reduced the oxidative damage in CRF rats. Moreover, transplantation with ICA-treated huMSCs decreased inflammatory responses, promoted the expression of growth factors, and protected injured renal tissues. Taken together, our findings suggest that ICA-treated huMSCs could improve the kidney function in CRF rats.

The immunomodulatory activities of licorice polysaccharides (Glycyrrhiza uralensis Fisch.) in CT 26 tumor-bearing mice.

BACKGROUND: The increasing use of complementary and alternative medicine (CAM) has kindled the need for scientific evaluation of the mechanism of action of CAMs. Although, licorice, a common ingredient in many Traditional Chinese medicine (TCM) has attracted great attention for its antitumor and immunomodulatory activities, the mechanism of action of its polysaccharides is still unclear. Here we report the immunomodulatory activity of licorice polysaccharides in vivo. METHODS: The differential anticancer activities of licorice polysaccharides by tumorigenesis and immunomodulation was evaluated in vivo. Six weeks old, 120 CT-26 tumor bearing BALB/c mice, weighing 20 ± 2 g were used. They were randomly divided into six groups, three groups receiving high molecular weight (fraction A), low molecular weight (fraction B) polysaccharides and crude extract (fraction C); positive, negative and normal groups receiving cytoxin, saline and normal diet respectively. Weight of mice and tumors was determined and tumorigenicity assay calculated to determine the anticancer effects. Immunomodulatory potential was determined by immune organ indices, immune cell population and serum cytokine levels using immune organ weight and index, flow cytometry and cytokine/chemokine bead panel kit respectively. RESULTS: Licorice polysaccharides exhibited immunomodulatory activities in CT 26 tumor bearing BALB/c mice. The polysaccharides significantly suppressed tumor growth and increased immune organ index. Furthermore, the immunomodulatory effect was evident with activation of CD4+ and CD8+ immune cells population. The polysaccharides also affected the production of various cytokines, by increasing IL 2, IL 6, IL 7 levels and a decreasing TNFα levels. CONCLUSION: In summary, licorice polysaccharide especially of low molecular weight exhibit anticancer and immunomodulatory activities by suppressing tumor growth and improving general health of mice. They also augment the thymus/spleen index and population of T lymphocytes. Furthermore, the polysaccharides enhance the levels of serum antitumor cytokines, IL 2, IL 6 and IL 7 while decreasing pro-tumor cytokine TNFα.

Immunomodulatory and anticancer potential of Gan cao (Glycyrrhiza uralensis Fisch.) polysaccharides by CT-26 colon carcinoma cell growth inhibition and cytokine IL-7 upregulation in vitro.

BACKGROUND: Chinese licorice, (Glycyrrhiza uralensis Fisch.) is one of the commonly prescribed herbs in Traditional Chinese Medicine (TCM). Gancao, as commonly known in China, is associated with immune-modulating and anti-tumor potential though the mechanism of action is not well known. In this study, we investigated the in vitro immunomodulatory and antitumor potential of Glycyrrhiza uralensis polysaccharides fractions of high molecular weight (fraction A), low molecular weight (fraction B) and crude extract (fraction C). METHODS: Cell proliferation and cytotoxicity was investigated using Cell Counting kit 8 (CCK-8) on Intestinal epithelial cell line (IEC-6) and Colon carcinoma cell line (CT-26). IL-7 gene expression relative to GAPDH was analysed using Real time PCR. The stimulation and viability of T lymphocytes was determined by Trypan blue exclusion assay. RESULTS: G.uralensis polysaccharides did not inhibit proliferation of IEC-6 cells even at high concentration. The ED50 was found to be 100 µg/ml. On the other hand, the polysaccharides inhibited the proliferation of cancer cells (CT-26) at a concentration of ≤50 µg/ml. Within 72 h of treatment with the polysaccharides, expression of IL-7 gene was up-regulated over 2 times. It was also noted that, IEC-6 cells secrete IL-7 cytokine into media when treated with G.uralensis polysaccharides. The secreted IL-7 stimulated proliferation of freshly isolated T lymphocytes within 6 h. The effect of the polysaccharides were found to be molecular weight depended, with low molecular weight having a profound effect compared to high molecular weight and total crude extract. CONCLUSION: Our findings indicate that G.uralensis polysaccharides especially those of low molecular weight have a potential as anticancer agents. Of great importance, is the ability of the polysaccharides to up-regulate anticancer cytokine IL-7, which is important in proliferation and maturation of immune cells and it is associated with better prognosis in cancer. Therefore, immunomodulation is a possible mode of action of the polysaccharides in cancer therapy.

Clinical effects of chemical drugs, fecal microbiota transplantation, probiotics, dietary fiber, and acupuncture in the treatment of chronic functional constipation: a systematic review and network meta-analysis.

Currently, there are increasingly diverse treatment modalities for chronic functional constipation (CFC). This study aims to compare the relative efficacy and safety of chemical drugs, fecal microbiota transplantation (FMT), probiotics, dietary fiber, and acupuncture in the treatment of patients with CFC. We searched relevant randomized controlled trials (RCTs) published in five databases up to November 2023. Network meta-analysis (NMA) was carried out using R Studio 4.2.1. Cumulative ranking probability plots, assessed through the surface under the cumulative ranking (SUCRA), were employed to rank the included drugs for various outcome measures. We included a total of 45 RCT studies with 17 118 patients with CFC. From the SUCRA values and NMA results FMT showed the best utility in terms of clinical efficacy, Bristol stool form scale scores, patient assessment of constipation quality of life scores, and the treatment modality with the lowest ranked incidence of adverse effects was electroacupuncture. Subgroup analysis of the chemotherapy group showed that sodium A subgroup analysis of the chemical group showed that sodium picosulfate 10 mg had the highest clinical efficacy. FMT is more promising in the treatment of CFC and may be more effective in combination with the relatively safe treatment of acupuncture.

Tissue damage from chronic liver injury inhibits peripheral NK cell abundance and proinflammatory function.

One of the difficulties in the treatment of hepatocellular carcinoma is that it is impossible to eliminate the inhibitory effect of the tumor microenvironment on immune response. Therefore, it is particularly important to understand the formation process of the tumor microenvironment. Chronic inflammation is the core factor of cancer occurrence and the leading stage of inflammation-cancer transformation, and the natural killer cell subsets play an important role in it. Our study confirmed that in the stage of chronic liver injury, the local immunosuppressive microenvironment of the liver (i.e. the damaged microenvironment) has been formed, but this inhibitory effect is only for peripheral natural killer cells and has no effect on tissue-resident natural killer subsets. The markers of damage microenvironment are the same as those of tumor microenvironment.

Differential expression of circular RNAs in human umbilical cord mesenchymal stem cells treated with icariin.

Human umbilical cord mesenchymal stem cells (hUMSCs) belong to a multipotent stem cell population. Transplantation of icariin (ICA)-treated hUMSCs have better tissue repairing function in chronic liver injury. This study was to investigate whether the tissue-repairing effects and migration of hUMSCs after ICA treatment were regulated by circular RNAs (circRNAs). ICA was used to treat hUMSCs in vitro for 1 week and the expression profiles of circRNAs were generated using RNA sequencing. Differentially expressed circRNAs in hUMSCs after ICA intervention were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were carried out to predict the potential function of dysregulated circRNAs. There were 52 differentially expressed circRNAs (32 circRNAs up-regulated and 20 circRNAs down-regulated) with fold change ≥2.0 before and after ICA treatment. ADP-ribosylation factors were associated with the dysregulated circRNAs among Gene Ontology analysis. Kyoto Encyclopedia of Genes and Genomes analysis showed that only endocytosis pathway was associated with up-regulated circRNAs, whereas 4 pathways including homologous recombination, RNA transport, axon guidance, and proteoglycans in cancer were related to down-regulated circRNAs. Fifty-two differentially expressed circRNAs and 238 predicted microRNAs were included in circRNAs-microRNAs network. The mechanism of ICA inducing hUMSCs migration may be through regulating circRNAs expression which affects ADP-ribosylation factors protein signal pathways.

Pro-inflammatory cytokines in stress-induced depression: Novel insights into mechanisms and promising therapeutic strategies.

Stress-mediated depression is one of the common psychiatric disorders with a high prevalence and suicide rate, there is a lack of effective treatment. Accordingly, effective treatments with few adverse effects are urgently needed. Pro-inflammatory cytokines (PICs) may play a key role in stress-mediated depression. Thereupon, both preclinical and clinical studies have found higher levels of IL-1ß, TNF-α and IL-6 in peripheral blood and brain tissue of patients with depression. Recent studies have found PICs cause depression by affecting neuroinflammation, monoamine neurotransmitters, hypothalamic pituitary adrenal axis and neuroplasticity. Moreover, they play an important role in the symptom, development and progression of depression, maybe a potential diagnostic and therapeutic marker of depression. In addition, well-established antidepressant therapies have some relief on high levels of PICs. Importantly, anti-inflammatory drugs relieve depressive symptoms by reducing levels of PICs. Collectively, reducing PICs may represent a promising therapeutic strategy for depression.

Immunosenescence: A new direction in anti-aging research.

The immune system is a major regulatory system of the body, that is composed of immune cells, immune organs, and related signaling factors. As an organism ages, observable age-related changes in the function of the immune system accumulate in a process described as 'immune aging. Research has shown that the impact of aging on immunity is detrimental, with various dysregulated responses that affect the function of immune cells at the cellular level. For example, increased aging has been shown to result in the abnormal chemotaxis of neutrophils and decreased phagocytosis of macrophages. Age-related diminished functionality of immune cell types has direct effects on host fitness, leading to poorer responses to vaccination, more inflammation and tissue damage, as well as autoimmune disorders and the inability to control infections. Similarly, age impacts the function of the immune system at the organ level, resulting in decreased hematopoietic function in the bone marrow, a gradual deficiency of catalase in the thymus, and thymic atrophy, resulting in reduced production of related immune cells such as B cells and T cells, further increasing the risk of autoimmune disorders in the elderly. As the immune function of the body weakens, aging cells and inflammatory factors cannot be cleared, resulting in a cycle of increased inflammation that accumulates over time. Cumulatively, the consequences of immune aging increase the likelihood of developing age-related diseases, such as Alzheimer's disease, atherosclerosis, and osteoporosis, among others. Therefore, targeting the age-related changes that occur within cells of the immune system might be an effective anti-aging strategy. In this article, we summarize the relevant literature on immune aging research, focusing on its impact on aging, in hopes of providing new directions for anti-aging research.

Associations of environmental factors with neurodegeneration: An exposome-wide Mendelian randomization investigation.

Neurodegenerative diseases (NDDs) remain a global health challenge. Previous studies have reported potential links between environmental factors and NDDs, however, findings remain controversial across studies and elusive to be interpreted as evidence of robust causal associations. In this study, we comprehensively explored the causal associations of the common environmental factors with major NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS), based on updated large-scale genome-wide association study data through two-sample Mendelian randomization (MR) approach. Our results indicated that, overall, 28 significant sets of exposure-outcome causal association evidence were detected, 12 of which were previously underestimated and newly identified, including average weekly beer plus cider intake, strenuous sports or other exercises, diastolic blood pressure, and body fat percentage with AD, alcohol intake frequency with PD, apolipoprotein B, systolic blood pressure, and forced expiratory volume in 1 s (FEV1) with ALS, and alcohol intake frequency, hip circumference, forced vital capacity, and FEV1 with MS. Moreover, the causal effects of several environmental factors on NDDs were found to overlap. From a triangulation perspective, our investigation provided insights into understanding the associations of environmental factors with NDDs, providing causality-oriented evidence to establish the risk profile of NDDs.

Role of epigenetics in the regulation of skin aging and geroprotective intervention: A new sight.

Multiple epigenetic factors play a regulatory role in maintaining the homeostasis of cutaneous components and are implicated in the aging process of the skin. They have been associated with the activation of the senescence program, which is the primary contributor to age-related decline in the skin. Senescent species drive a series of interconnected processes that impact the immediate surroundings, leading to structural changes, diminished functionality, and heightened vulnerability to infections. Geroprotective medicines that may restore the epigenetic balance represent valid therapeutic alliances against skin aging. Most of them are well-known Western medications such as metformin, nicotinamide adenine dinucleotide (NAD+), rapamycin, and histone deacetylase inhibitors, while others belong to Traditional Chinese Medicine (TCM) remedies for which the scientific literature provides limited information. With the help of the Geroprotectors.org database and a comprehensive analysis of the referenced literature, we have compiled data on compounds and formulae that have shown potential in preventing skin aging and have been identified as epigenetic modulators.