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• Overview of tumor-specific neoantigens as targets for personalized cancer therapies and their role in immune system recognition. • Discussion of clinical trials using neoantigens in cancer immunotherapy and the challenges posed by tumor heterogeneity and immune tolerance. • To explore advanced technologies for neoantigen identification and future strategies to improve their clinical application. Neoantigen, unique peptides resulting from tumor-specific mutations, represent a promising frontier in oncology for personalized cancer immunotherapy. Their unique features allow for the development of highly specific and effective cancer treatments, which can potentially overcome the limitations of conventional therapies. This paper explores the current prospects and challenges associated with the application of neoantigens in oncology. We examine the latest advances in neoantigen identification, vaccine development, and adoptive T cell therapy. Additionally, we discuss the obstacles related to neoantigen heterogeneity, immunogenicity prediction, and the tumor microenvironment. Through a comprehensive analysis of current research and clinical trials, this paper aims to provide a detailed overview of how neoantigens could revolutionize cancer treatment and the hurdles that must be overcome to realize their full potential. [ABSTRACT FROM AUTHOR]

• An introduction to the three major mechanisms of metabolic reprogramming in thyroid cancer and their impact on the immune microenvironment. • The mechanism of metabolic reprogramming promoting the development of thyroid cancer was introduced. • This paper introduces the therapeutic measures of immunotherapy for thyroid cancer targeting metabolic alterations. The metabolic reprogramming of cancer cells is a hallmark of many malignancies. To meet the energy acquisition needs of tumor cells for rapid proliferation, tumor cells reprogram their nutrient metabolism, which is caused by the abnormal expression of transcription factors and signaling molecules related to energy metabolic pathways as well as the upregulation and downregulation of abnormal metabolic enzymes, receptors, and mediators. Thyroid cancer (TC) is the most common endocrine tumor, and immunotherapy has become the mainstream choice for clinical benefit after the failure of surgical, endocrine, and radioiodine therapies. TC change the tumor microenvironment (TME) through nutrient competition and metabolites, causing metabolic reprogramming of immune cells, profoundly changing immune cell function, and promoting immune evasion of tumor cells. A deeper understanding of how metabolic reprogramming alters the TME and controls immune cell fate and function will help improve the effectiveness of TC immunotherapy and patient outcomes. This paper aims to elucidate the metabolic communication that occurs between immune cells around TC and discusses how metabolic reprogramming in TC affects the immune microenvironment and the effectiveness of anti-cancer immunotherapy. Finally, targeting key metabolic checkpoints during metabolic reprogramming, combined with immunotherapy, is a promising strategy. [ABSTRACT FROM AUTHOR]

• Inhibited autophagy enhances the sensitivity of IDA to FAT1-L AML. • Inhibiting autophagy weakens the CD8+ T cell infiltration in FAT1-L AML. • Inhibiting autophagy upregulates PD-L1 by decreasing its autophagic degradation. • PD-L1 inhibitors reverse the CQ-induced decrease in CD8+ T-cell infiltration in AML. • FAT1 decreased ATG10 transcription and subsequently inhibited AML autophagy. Both Autophagy and FAT atypical cadherin 1 (FAT1) regulates the chemosensitivity and immune escape of tumour cells. Our previous paper showed that FAT1 decreased acute myeloid leukemia (AML) autophagy by inhibiting the TGFβ-Smad2/3 pathway. This study builds upon our previous paper and aims to explore whether FAT1-inhibited autophagy is involved in regulating chemosensitivity and immune escape in AML. We validated the inhibitory effect of FAT1 on AML autophagy through western blot, qPCR, and luciferase reporter assays. In addition, we explored the effect of FAT1-inhibited autophagy on idarubicin (IDA) sensitivity and AML immune escape through caspase-3 activity analysis, trypan blue exclusion assays, and flow cytometry. We demonstrated for the first time that the autophagy inhibitor chloroquine (CQ) enhances the cytotoxic effect of IDA on FAT1-low-expressing (FAT1-L) AML cells. We also found that CQ weakened CD8+ T cell infiltration in FAT1-L AML cells. Further research revealed that CQ upregulated PD-L1 protein levels by decreasing its autophagic degradation and that the PD-L1 inhibitor atezolizumab reversed the decrease in CD8+ T cell infiltration caused by CQ in FAT1-L AML cells. In addition, we found that FAT1 decreased autophagy related 10 (ATG10) transcription, leading to decreased AML autophagy. These results revealed that in FAT1-L AML cells, inhibiting autophagy by CQ enhances the cytotoxic effect of IDA, but leads to immune escape, resulting in AML recurrence. Our study supports the use of a combination of autophagy and PD-L1 inhibitors with IDA to increase the cytotoxic effect of IDA while inhibiting AML recurrence. [ABSTRACT FROM AUTHOR]

• The present paper is of significant relevance in finding novel and effective weapons originating from Traditional Chinese Medicine and Ayurveda to address the molecular heterogeneity of cancer and at the same time projecting Withania somnifera (WS) as a potent phytoestrogen. • Also significant advancements in pharmacology and drug technology aimed at improving the efficacy of cancer therapies and extending the life expectancy of patients diagnosed with malignancy. It emphasizes the gender disparity in breast cancer occurrence, with the female gender being the primary risk factor. • Withania somnifera (WS), commonly known as Indian ginseng, has garnered attention for its traditional use in treating various ailments. Recent research has demonstrated promising anti-breast cancer properties of WS and its phytoconstituents. These findings suggest the potential of WS as both a prophylactic and therapeutic adjunct to standard breast cancer treatments. The review delves into the experimental evidence supporting the use of WS in breast cancer management, shedding light on its molecular mechanisms and targets. • The review explores the broader implications of WS in hormonally-induced cancers, including ovarian, uterine, and cervical cancers. By elucidating the multiple molecular mechanisms through which WS acts against these cancers, the review aims to provide insights into breast cancer progression and metastasis. • Moreover, WS is not recognized as a phytoestrogen-rich herb, however, some studies suggests it may exhibit estrogenic properties. These potential highlights include its ability to modulate hormonal balance, support reproductive health and alleviate symptoms associated with hormonal imbalances. Also, a few papers of this type have been published in the journal in the last few years. Therefore, the present review highlights the unexplored potential of WS, which might significantly contribute towards the pleiotropic potential of WS. Major significant advancements in pharmacology and drug technology have been made to heighten the impact of cancer therapies, improving the life expectancy of subjects diagnosed with malignancy. Statistically, 99% of breast cancers occur in women while 0.5–1% occur in men, the female gender being the strongest breast cancer risk factor. Despite several breakthroughs, breast cancer continues to have a worldwide impact and is one of the leading causes of mortality. Additionally, resistance to therapy is a crucial factor enabling cancer cell persistence and resurgence. As a result, the search and discovery of novel modulatory agents and effective therapies capable of controlling tumor progression and cancer cell proliferation is critical. Withania somnifera (L.) Dunal (WS), commonly known as Indian ginseng, has long been used traditionally for the treatment of several ailments in the Indian context. Recently, WS and its phytoconstituents have shown promising anti-breast cancer properties and, as such, can be employed as prophylactic as well as therapeutic adjuncts to the main line of breast cancer treatment. The present review is an attempt to explore and provide experimental evidences in support of the prophylactic and therapeutic potential of WS in breast cancer, along with a deeper insight into the multiple molecular mechanisms and novel targets through which it acts against breast and other hormonally-induced cancers viz. ovarian, uterine and cervical. This exploration might prove crucial in providing better understanding of breast cancer progression and metastasis and its use as an adjunct in improving disease prognosis and therapeutic outcome. [ABSTRACT FROM AUTHOR]

• CAR-T therapy offers durable remissions in refractory hematological malignancies. • Meta-analyses show significant efficacy in various hematologic cancers. • CAR T-cell therapy improves quality of life for blood cancer patients. • Encouraging results in CD22-targeting CAR T-cell therapy for B-cell malignancies. • Long-term studies reveal durable remissions but also persistent adverse effects. Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a groundbreaking and highly promising approach for the management of cancer. This paper reviews the efficacy of CAR-T therapy in the treatment of various hematological malignancies, also, with a mention of its effect on solid tumors, for which they have not received FDA approval yet. Different common and uncommon side effects are also discussed in this paper, with attention to the effect of each drug separately. By reviewing the recommendations of the FDA for CAR-T therapy research, we have extensively discussed dose-limiting toxicities. This further highlights the need for precise dosing strategies, striking a balance between therapeutic benefits and potential risks. Additionally, we reviewed the long-term follow-up of patients receiving CAR-T therapy to gain valuable insights into response durability and late-onset effects. [ABSTRACT FROM AUTHOR]

[Display omitted] • Immune and inflammation-mediated disorders are key contributors to SNHL development. • Dysregulated inflammatory mediators and chemokines induce chronic cochlear inflammation. • Genetic mutations, such as TMPRSS3 and connexin genes, modulate cochlear inflammation. • Cochlear inflammatory responses directly impair auditory function, causing hearing loss. • Gene therapy holds promise for targeted treatment of SNHL by addressing inflammation. Sensorineural hearing loss (SNHL) is a prevalent clinical condition primarily attributed to dysfunction within various components of the auditory pathway, spanning from the inner ear to the auditory cortex. Recent research has illuminated immune and inflammation-mediated disorders of the inner ear as critical contributors to SNHL. Disruptions in the equilibrium of inflammatory mediators, chemokines, the complement system, and inflammatory vesicles within the cochlea provoke aberrations in immune cell activity, fostering a chronic pro-inflammatory milieu that detrimentally affects the structural and functional integrity of the inner ear, culminating in hearing impairment. Specific genetic mutations, especially those affecting auditory structures, play an important role in SNHL. These mutations regulate inflammatory mediators and cellular responses, thereby altering the inflammatory dynamics within the cochlea. This review delves into the pathogenesis of sensorineural hearing loss, emphasizing the impact of genetic alterations, immune responses within the inner ear, and inflammatory mediators on auditory function. It highlights the significance of Transmembrane Serine Protease 3 (TMPRSS3) and connexin gene mutations as pivotal genetic elements in SNHL, underscoring the central role of inflammatory responses in cochlear damage. Furthermore, the paper discusses the promise of gene therapy and targeted molecular interventions, underscoring the necessity for continued exploration into the specific actions of various inflammatory agents to refine personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]

• M2 macrophage polarization is linked to type 2 inflammation and allergic severity. • Tet2 regulates 5-methylcytosine (m5C) oxidation in mRNA, similar to its function in DNA, highlighting a new regulatory mechanism. • Tet2 alleviates allergic severity and M2 polarization. • Tet2 deficiency reduces mRNA m5C demethylation of Klf4 and Rock1, promoting M2 polarization in allergies, offering new protective insights. Allergic rhinitis (AR) represents a hallmark of obvious hypersensitivity with an imbalance of immune responses, including abnormal macrophage activity in local tissues. It has been reported that alternatively activated macrophages (M2) may contribute to allergic pathogenesis. Ten-eleven translocation (Tet) enzymes can oxidize 5-methylcytosine (m5C) in mRNA, implying the epigenetic regulation of post-transcriptional RNA modification. Our previous study suggested that decreased Tet2 impairs the function of regulatory T cells, failing to exert a protective role in AR. However, the mechanism of Tet2 in macrophage polarization has been little discussed. In this paper, we investigate the regulatory role of Tet2 in macrophage polarization under allergic inflammation. Macrophage immunofluorescence and eosinophil counts were used to confirm the inflammatory and polarized state in the nasal mucosa of AR patients. Additionally, we used Raw264.7 cells to explore the relationships among mRNA methylation, Tet2 expression, and the macrophage polarization process. Furthermore an Ovalbumin (OVA)-mediated AR mouse model was established with wild-type (WT) and Tet2 gene knockout (Tet2−/−) mice to verify the role of Tet2 in AR severity and macrophage polarization. The final stage comprised RNA sequencing, methylated RNA immunoprecipitation with qPCR (MeRIP-qPCR) using bone marrow-derived macrophages (BMDMs) from WT and Tet2−/− mice to explore the effect of Tet2 deficiency on the mRNA methylation level of M2-related genes under OVA treatment. A two-tailed Student's t -test was used to compare two groups, and Spearman correlation analysis was applied for relationship analysis. M2-macrophages were confirmed as the dominant subtype associated with eosinophil levels in AR nasal tissues. In vitro analyses demonstrated that mRNA methylation and Tet2 are linked to M2 macrophages. Additionally, we found that Tet2 influences local allergic severity and macrophage polarization. Specifically, Tet2 deficiency decreased the mRNA m5C demethylation levels of Klf4 and Rock1, contributing to M2 polarization in an allergic state. The findings of this study demonstrate that Tet2 may play a protective role in AR by negatively regulating M2-related factors through mRNA m5C demethylation. These findings provide new insights into AR therapy, suggesting that intervening in macrophage polarization at the post-transcriptional level could be a novel therapeutic strategy. [ABSTRACT FROM AUTHOR]

• This paper provides an update on the cGAS-STING signaling pathway and its regulatory role in colorectal cancer (CRC) immune microenvironment. • The potential of cGAS-STING as a therapeutic target for CRC was discussed. • The current status of CRC immunotherapy based on cGAS-STING signaling pathway was summarized. • The clinical therapeutic potential of targeting the cGAS-STNG signaling pathway in CRC was emphasized. • The current clinical research status and therapeutic potential of STING agonists developed for cGAS-STING signaling pathway were discussed. Colorectal cancer (CRC) is a common malignant tumor in the gastrointestinal tract, it is known as the "silent killer", which poses a serious threat to the lives of patients. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon gene (STING) signaling pathway responds to DNA by sensing, which plays an important role in anti-infection, autoimmune diseases and anti-tumor immunity. Recent studies have found that the activation of cGAS-STING pathway in CRC can induce the expression and secretion of type I interferon (IFN-I) and a variety of inflammatory factors, further activate anti-tumor CD8+ T cells, exert anti-tumor immune response, and inhibit the progression of CRC. Therefore, targeting the cGAS-STING pathway and developing drugs that can regulate the cGAS-STING pathway are of great significance for improving the therapeutic effect and prognosis of CRC patients. In this review, we introduce the cGAS-STING signaling pathway and the regulatory role of this signaling pathway in CRC immune microenvironment. In addition, we discussed the research progress of cGAS-STING pathway in CRC immunotherapy and the clinical research status of STING agonists developed against this pathway, emphasizing the clinical potential of CRC immunotherapy based on the cGAS-STING signaling pathway. [ABSTRACT FROM AUTHOR]

• This paper summarizes the sources and characteristics of CAFs. • We also review the mechanism of CAFs promoting tumor cell metastasis. • More importantly, we explore the value of targeted CAFs for clinical practice. Cancer-associated fibroblasts (CAFs), which are the most frequent stromal cells in the tumor microenvironment (TME), play a key role in the metastasis of tumor cells. Generally speaking, CAFs in cooperation with tumor cells can secrete various cytokines, proteins, growth factors, and metabolites to promote angiogenesis, mediate immune escape of tumor cells, enhance endothelial-to-mesenchymal transition, stimulate extracellular matrix remodeling, and preserve tumor cell stemness. These activities of CAFs provide a favorable exogenous pathway for tumor progression and metastasis, and a microenvironment that allows rapid growth of tumor cells, which always lead to poor prognosis for patients. More importantly, it seems that targeting CAFs is also a potential precision therapeutic strategy in clinical practice. Hence, this review outlines the origin of CAFs, the relationship between CAFs and cancer metastasis, and targeting CAFs as a potential strategy for cancer patients, which could give some inspirations for cancer treatment in clinic. [ABSTRACT FROM AUTHOR]

[Display omitted] • LPS-induced lethality and inflammation are markedly reduced in CD36 knockout mice. • CD36 knockout mice exhibit a reduction in CerS6 protein expression. • CD36 inhibition increases ubiquitination and proteasomal degradation of CerS6. • CerS6-derived C16-ceramide contributes to LPS-induced inflammation via ER stress. • ER stress is an upstream regulator of inflammatory cascades such as NF-κB and iNOS. The type 2 scavenger receptor CD36 functions not only as a long chain fatty acid transporter, but also as a pro-inflammatory mediator. Ceramide is the simple N -acylated form of sphingosine and exerts distinct biological activity depending on its acyl chain length. Six ceramide synthases (CerS) in mammals determine the chain length of ceramide species, and CerS6 mainly produces C16-ceramide. Endotoxin-induced septic shock shows high mortality, but the pathophysiologic role of sphingolipids involved in this process has been hardly investigated. This paper aims to highlight the different role of CerS isoforms in endotoxin-induced inflammatory responses and the regulatory role of CD36 in CerS6 protein degradation with an emphasis as the potential therapeutic candidates in humans. Lipopolysaccharide (LPS), the endotoxin of the Gram-negative bacterial cell wall, was treated to induce endotoxin-induced inflammation both in vitro and in vivo. CerS6-derived C16-ceramide propagated LPS-induced inflammatory responses activating various intracellular signaling pathways, such as mitogen-activated protein kinase and nuclear factor-κB, resulting in the formation of inflammasome complex and pro-inflammatory cytokines. Mechanistically, CerS6-derived C16-ceramide augmented inflammatory responses via endoplasmic reticulum stress, and CerS6 protein stability was regulated by CD36. Finally, CerS6 protein expression and LPS-induced lethality were strikingly reduced in CD36 knockout mice. Collectively, our findings show that CerS6-derived C16-ceramide plays a pivotal role in endotoxin-induced inflammation and suggest CerS6 and its regulator CD36 as possible targets for therapy under life-threatening inflammation such as septic shock. [ABSTRACT FROM AUTHOR]

[Display omitted] • The potential link between AGEs, RAGE, and oxidative stress is deeply explored. • AGEs-RAGE oxidative stress axis as a causative factor in diabetes is identified. • Natural polysaccharides ameliorating diabetes through the axis is summarized. Diabetes mellitus, a chronic metabolic disorder, poses a significantly public health challenge. Extensive research highlights that contemporary dietary patterns, characterized by excessive intake of sugar, fat, and protein, are major contributors to the onset and progression of diabetes. The central element to this process is the aberrant activation of the advanced glycation end products (AGEs) – receptor for AGEs (RAGE) – oxidative stress axis, which plays a pivotal role in disrupting normal carbohydrate metabolism. This pathway presents a critical target for developing interventions aimed at mitigating diabetes and its complications. In recent years, natural polysaccharides have emerged as promising agents in the prevention and treatment of diabetes, due to their ability to inhibit AGE formation, regulate RAGE expression, and modulate the AGEs-RAGE-oxidative stress axis. In this paper, we explore the pathogenic mechanism of this axis and review the therapeutic potential of natural polysaccharides in managing diabetes and its complications. Our goal is to provide new insights for the effective management of diabetes and its associated health challenges. [ABSTRACT FROM AUTHOR]

• Summarizes structural design strategies for bispecific CAR-Ts available by the end of 2023. • Reviews antigen-targeting selection strategies in B-cell related tumors such as B-ALL, NHL, and MM. • Summarizes design approaches of CARs targeting same and different disease antigens, highlighting the impact of scFv, transmembrane domains, hinge regions, and co-stimulatory domains on bispecific CAR-T efficacy. • Summarizes the advantages and disadvantages of various bispecific CAR-Ts and outlines future research trends. Single-targeted CAR-T has exhibited notable success in treating B-cell tumors, effectively improving patient outcomes. However, the recurrence rate among patients remains above fifty percent, primarily attributed to antigen escape and the diminished immune persistence of CAR-T cells. Over recent years, there has been a surge of interest in bispecific CAR-T cell therapies, marked by an increasing number of research articles and clinical applications annually. This paper undertakes a comprehensive review of influential studies on the design of bispecific CAR-T in recent years, examining their impact on bispecific CAR-T efficacy concerning disease classification, targeted antigens, and CAR design. Notable distinctions in antigen targeting within B-ALL, NHL, and MM are explored, along with an analysis of how CAR scFv, transmembrane region, hinge region, and co-stimulatory region design influence Bi-CAR-T efficacy across different tumors. The summary provided aims to serve as a reference for designing novel and improved CAR-Ts, facilitating more efficient treatment for B-cell malignant tumors. [ABSTRACT FROM AUTHOR]

BTK plays a pivotal role in the B cell signaling, abnormal activation of which is associated with the progression of SLE or other diseases. Targeting BTK has emerged as a promising therapeutic strategy for SLE. [Display omitted] • BTK is a key kinase downstream of BCR, FcR and multiple pathways. • Overactivated BTK contributes to SLE development by driving B cell abnormalities. • Inhibitors targeting BTK are a promising and effective option for SLE treatment. Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disorder involving multiple organs and systems. There is growing evidence that autoreactive B cells occupy a central role in the occurrence and progression of SLE due to their ability to generate pathogenic autoantibodies. Small molecule inhibitors targeting Bruton's tyrosine kinase (BTK), a crucial intracellular kinase regulating B cell development and function, emerge as a new strategy to treat SLE in recent years and are superior to biologic agents depleting B cells in many aspects. Supportive data obtained from lupus-prone mice preliminarily demonstrated the promising therapeutic potential of BTK inhibition. However, these BTK inhibitors, including elsubrutinib, evobrutinib, etc., mostly face with unsatisfactory efficacy and certain safety issues during clinical use, driving the quest for new-generation inhibitors with improved potency and higher selectivity. This paper elaborates the importance of BTK involvement in SLE pathogenesis, reviews the clinical research progress of BTK inhibitors for SLE and discusses limitations and challenges the drugs met in development, in order to contribute to a deeper understanding of disease mechanism and provide a reference for new-generation BTK inhibitor research. [ABSTRACT FROM AUTHOR]

• Signal transduction pathway of STAT3 is related to Alzheimer's disease. • Twenty-two compounds from natural products alleviate Alzheimer's disease by inhibiting STAT3 in microglia and astrocytes. • Three compounds from natural products alleviate Alzheimer's disease by activating STAT3 in neurons. Alzheimer's disease (AD) is a neurodegenerative disorder that is difficult to cure and of global concern. Neuroinflammation is closely associated with the onset and progression of AD, making its treatment increasingly important. Compounds from natural products, with fewer side effects than synthetic drugs, are of high research interest. STAT3, a multifunctional transcription factor, is involved in various cellular processes including inflammation, cell growth, and apoptosis. Its activation and inhibition can have different effects under various pathological conditions. In AD, the STAT3 protein plays a crucial role in promoting neuroinflammation and contributing to disease progression. This occurs primarily through the JAK2-STAT3 signaling pathway, which impacts microglia, astrocytes, and hippocampal neurons. This paper reviews the STAT3 signaling pathway in AD and 25 compounds targeting STAT3 up to 2024. Notably, Rutin, Paeoniflorin, and Geniposide up-regulate STAT3 in hippocampal and cortex neurons, showing neuroprotective effects in various AD models. Other 23 compounds downregulate AD by suppressing neuroinflammation through inhibition of STAT3 activation in microglia and astrocytes. These findings highlight the potential of compounds from natural products in improving AD by targeting STAT3, offering insights into the prevention and management of AD. [ABSTRACT FROM AUTHOR]

• SCFAs participate in host immunomodulation through activation of GPCRs and inhibition of HDACs. • The involvement of SCFAs in the pathogenesis of psoriasis may be exerted through the regulation of intestinal barrier integrity and modulation of the immune system. • In innate immunity, SCFAs affect neutrophil recruitment, regulate macrophage polarization, and influence dendritic cell maturation; in adaptive immunity, they promote the differentiation of T cells to Tregs and B cells to Bregs, thus participating in immune and inflammatory responses. Psoriasis is a prevalent chronic inflammatory and immunological disorder. Its lesions are present as scaly erythema or plaques. Disruptions in the body's immune system play a significant role in developing psoriasis. Recent evidence suggests a potential role of the gut microbiome in autoimmune diseases. Short-chain fatty acids (SCFAs) are the primary metabolites created by gut microbes and play a crucial fuction in autoimmunity. SCFAs act on various cells by mediating signaling to participate in host physiological and pathological processes. These processes encompass body metabolism, maintenance of intestinal barrier function, and immune system modulation. SCFAs can regulate immune cells to enhance the body's immune function, potentially influencing the prevention and treatment of psoriasis. However, the mechanisms underlying the role of SCFAs in psoriasis remain incompletely understood. This paper examines the relationship between SCFAs and psoriasis, elucidating how SCFAs influence the immune system, inflammatory response, and gut barrier in psoriasis. According to the study, in psoriasis, SCFAs have been shown to regulate neutrophils, macrophages, and dendritic cells in the adaptive immune system, as well as T and B cells in the innate immune system. Additionally, we explore the role of SCFAs in psoriasis by maintaining intestinal barrier function, restoring intestinal ecological homeostasis, and investigating the potential therapeutic benefits of SCFAs for psoriasis. [ABSTRACT FROM AUTHOR]

[Display omitted] • We captures BKV research status, advances, and offers new perspectives for future challenges. • Focus on improving transplant prevention, clinical education, and medical compliance until effective antivirals emerge. • New preventive, diagnostic, and therapeutic measures in our paper bring new insights to clinicians. Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges. [ABSTRACT FROM AUTHOR]

In recent years, the research on the pathogenesis of systemic lupus erythematosus (SLE) has been deepened, from the level of histopathology to the cellular and molecular biology, thus promoting the progress of SLE drug therapeutics. In March 2011, the United States Food and Drug Administration (FDA) approved the humanized monoclonal antibody, Belimumab for the treatment of SLE and put an end to the dilemma of no new drug available to SLE for more than half a century. On the other hand, the continuous evidence-based medical information has enabled rheumatologists to have a more comprehensive and depth understanding of the application of SLE traditional therapies, further improve the treatment strategy of SLE and put forward higher requirements for treatment goals. At the same time, advances in therapies have significantly improved survival rate of the patients, and the importance of long-term complications such as early-onset atherosclerosis and cardiovascular events has become increasingly apparent as a new challenge. In view of the hot issues of SLE clinical treatment, this paper introduces the research progress in recent years. • The advanced treatment in SLE is presented. • This paper introduces treatment strategies for SLE and prevention of cardiovascular complications. • This paper sets up the general arrangement for the treatment of SLE. [ABSTRACT FROM AUTHOR]

• Dual regulatory roles of lncRNA and miRNA. • Mechanisms of action in osteosarcoma. • Potential biomarkers for prognosis and therapy. • Emerging therapeutic strategies. Osteosarcoma is a common primary malignant bone tumor with a high incidence in children and adolescents, with high invasiveness and lung metastases. Even after traditional surgical excision, chemoradiotherapy, and comprehensive treatment, the survival rate of patients is still low, and the prognosis is not ideal. As an important part of non-coding RNA family, lncRNA and miRNA have significant regulatory effects on the growth, proliferation, metastasis and apoptosis of osteosarcoma cells. Therefore, exploring the roles of lncRNAs and miRNAs in the occurrence and development of osteosarcoma is of great help for the subsequent diagnosis, treatment, and prognosis of osteosarcoma. This paper mainly reviews the current research progress on the effects and mechanisms of lncRNAs and miRNAs on osteosarcoma cells, in order to provide new ideas for future research on the development process, treatment methods, and prognosis of osteosarcoma. [ABSTRACT FROM AUTHOR]

[Display omitted] • Ion channels play a pivotal role in the regulation of macrophage function. • Ion channels in macrophages show various effects in a variety of diseases. • Targeting ion channels in macrophages has therapeutic potential for the treatment of related diseases. Macrophages are immune cells found throughout the body and exhibit morphological and functional diversity. Macrophages have been implicated in a wide range of diseases, including autoimmune diseases, acute liver injury, cardiovascular diseases, lung diseases and tumours. Ion channels are transmembrane glycoproteins with important functions in maintaining homeostasis in the intra- and extracellular environment and mediating signal transduction. Many studies have shown that different types of ion channels influence the role of macrophages in the development of various diseases. In recent years, studies on the role of ion channels in macrophages in immune regulation and inflammatory responses have attracted much attention. In order to gain a deeper understanding of the role of macrophage ion channels, this paper reviews the recent research progress on the role of macrophage ion channels in recent years. The aim is to explore the role of different ion channels in the regulation of macrophage function and their impact on a variety of disease processes. The most studied channels are calcium, sodium and potassium channels, most of which are located in the cell membrane. Among these, TRP channels have a more complex role in M1 and M2 macrophage types. Ion channels are critical for the functional regulation of macrophages. Targeting ion channels provides new avenues for disease prevention and treatment. This review provides researchers with new ideas and introduces readers to the current state of research on ion channels in macrophages. [ABSTRACT FROM AUTHOR]

Two Epimedium-derived isomeric flavonoids, CIT and IT, had the therapeutic effect in osteopenic rats. However, it is difficult to expound their activity differences in anti-osteoporosis. This paper contrasted their anti-osteoporosis activity from the perspective of their affinity to OPG/RANKL protein targets. Molecular docking indicated that both of CIT and IT could interact with the hydrophobic pockets of OPG/RANKL, while CIT was easier and more stable to combine with RANKL. On the contrary, compared with CIT, IT was more inclined to combine with OPG and stay away from combining with RANKL. Subsequently, whether the interaction between isomeric flavonoids and OPG/RANKL targets promoted or suppressed bone resorption was undefined and which was validated by zebrafish embryo and ovariectomized rats in this paper. Compared with IT, the staining area and cumulative optical density of zebrafish skeleton were significantly increased after the treatment of CIT (0.1 μM, p  < 0.05). Furthermore, CIT mainly reflected a more significant role in upregulating OPG ( p  < 0.05), downregulating RANKL ( p  < 0.05), reducing serum AKP and TRACP level ( p  < 0.05), enhancing bone biomechanical properties ( p  < 0.05), increasing bone mineral density ( p  < 0.05) and improving trabecular bone microarchitecture ( p  < 0.05) in osteoporotic rats. In conclusion, the combination of isomeric flavonoids (CIT/IT) and OPG/RANKL targets attenuated the excitation effects of OPG or RANKL on RANKL. Because CIT was more firmly combined with RANKL than IT, CIT had stronger anti-osteoporosis effect by inhibiting bone resorption. [ABSTRACT FROM AUTHOR]

[Display omitted] • CKLF1 shows various effects on different types of cells involved in cardiovascular and cerebrovascular diseases. • CKLF1 plays complex and dynamic roles in diverse cardiovascular and cerebrovascular diseases. • Targeting CKLF1 has therapeutic potential for treating cardiovascular and cerebrovascular diseases. Chemokine like factor 1 (CKLF1) is a novel atypical chemokine, playing a crucial role in cardiovascular and cerebrovascular diseases (CCVDs) demonstrated by a growing body of works. In cardiovascular diseases including atherosclerosis and myocardial infarction, meanwhile in cerebrovascular diseases such as ischemic stroke and hemorrhagic stroke, the expression levels of CKLF1 change markedly, which triggers downstream signaling pathways by binding with its functional receptors, and then exerts multiple effects to participate in the occurrence and development of these CCVDs. The functional roles of CKLF1 are dynamic and CKLF1 may act as a double-edged sword. The CCVDs-promoting role is related to recruiting inflammatory cells, enhancing the proliferation of vascular smooth muscle cells and endothelial cells, while the CCVDs-suppressing role may correlate with migration of nerve cells and promotion of hematopoietic stem cell proliferation which contributes to disease recovery. Based on this, the paper intends to review expression shifts, potential roles, and molecular mechanisms of CKLF1 in CCVDs, and the current status of CKLF1 targeted therapeutic strategies is also included. We hope this review may provide a valuable reference for using CKLF1 as a diagnostic and prognostic biomarker for CCVDs or developing novel treatments. [ABSTRACT FROM AUTHOR]

• VISTA is an inhibitory immune checkpoint that acts as a ligand or receptor to exert immunosuppressive effects. • Abnormal overexpression of VISTA in gynecological tumors promotes tumor progression. Immune checkpoint blockade (ICB) therapy has revolutionized cancer treatment but has shown limited efficacy in gynecologic cancers. VISTA (V-domain Ig suppressor of T-cell activation), a member of the B7 family, is emerging as another checkpoint that regulates the anti-tumor immune responses within the tumor microenvironment. This paper reviews the structure, expression, and mechanism of action of VISTA. Furthermore, it highlights recent advances in VISTA-blocking therapies and their potential in improving outcomes for patients with gynecologic cancers. By understanding the role of VISTA in mediating the immune evasion of gynecologic tumors, we can develop more effective combinatory treatment strategies that could overcome resistance to current ICB therapies. [ABSTRACT FROM AUTHOR]

• Aptamer-mediated nanomedicines could enhance the accuracy of drug delivery and target drug delivery to tumor sites, reducing side effects. • Aptamer-mediated photodynamic therapy could more precisely deliver photosensitizers to tumor cells, reducing toxicity to normal tissues. • Aptamer-mediated photothermal therapy could enable the light source to more accurately locate and convert light energy into heat energy, causing local temperature rise, thereby eliminating cancer cells and effectively reducing the adverse effects on normal tissues. • Immunotherapy combined with aptamers could more accurately identify and modulate immune cells in the tumor microenvironment, enhancing anti-tumor immune responses and protecting normal tissues. The treatment of tumors still faces considerable challenges. While conventional treatments such as surgery, chemotherapy, and radiation therapy provide some curative effects, their side effects and limitations highlight the importance of finding more precise treatment strategies. Aptamers have become an important target molecule in the field of drug delivery systems due to their good affinity and targeting, and they have gradually become an important link from basic research to clinical application. In this paper, we discussed the latest progress of aptamer-mediated nanodrugs, as well as aptamer-mediated photodynamic therapy, photothermal therapy, and immunotherapy strategies for tumor treatment, and explored the possibility of aptamer-mediated therapy for accurate tumor treatment. The purpose of this review is to provide novel insights for treating tumors with aptamer-mediated therapies by summarizing these innovative strategies, thereby ultimately enhancing the therapeutic efficacy for cancer patients. [ABSTRACT FROM AUTHOR]

• This paper provides a new theoretical framework from disease-related biomolecules to treatment progress. • This paper further collected evidence for the conclusion that psoriasis is an autoimmune disease. • This paper summarizes the development of biologic therapies for psoriasis and psoriatic arthritis. Over the past half century, psoriasis is considered as an immune-mediated inflammatory skin disease with the combined hallmarks of autoimmunity and autoinflammation, according to growing volumes of clinical and experimental findings. There is currently no cure for psoriasis, current treatment strategies focus on symptom control, disease minimization, and patient's quality of life enhancement. To meet these challenges, it keeps imperative to discover potential biomarkers, so that not only can they be used for the prediction and monitoring of psoriasis disease in clinic, but also can provide novel therapeutic targets or treatment strategies for psoriasis sufferers. This review systematically demonstrates the research progress of psoriasis-related biomarkers and elaborates their related mechanisms in the pathological development of psoriasis and psoriatic arthritis. In addition, we summarize the development of biologic therapies for psoriasis and psoriatic arthritis in order to drive the broader discussion of psoriasis as an autoimmune-mediated inflammatory skin disease. [ABSTRACT FROM AUTHOR]

• CD24 and CSC: Few previous studies have summarized the relationship between CD24 and corresponding cancer stem cells. This review summarizes the reported CD24-related tumor stem cells so far. • CD24 and tumor progression: CD24, as a kind of innate immune checkpoints, not only can be mediated tumor cell immune escape, also can promote the proliferation and metastasis of tumor cells, this paper summarizes the current related studies of CD24 promote tumor progression, indicate its potential as a cancer related molecules, provides a theoretical basis for future targeted therapies. • CD24 is involved in drug resistance of tumor cells: Chemotherapy resistance is a common problem in tumor treatment. Studies have found that CD24 may promote tumor drug resistance after chemotherapy. This paper summarizes the post chemotherapy drug resistance of tumors related to CD24 for the first time. The CD24 protein is a heat-stable protein with a small core that undergoes extensive glycosylation. It is expressed on the surface of various normal cells, including lymphocytes, epithelial cells, and inflammatory cells. CD24 exerts its function by binding to different ligands. Numerous studies have demonstrated the close association of CD24 with tumor occurrence and progression. CD24 not only facilitates tumor cell proliferation, metastasis, and immune evasion but also plays a role in tumor initiation, thus, serving as a marker on the surface of cancer stem cells (CSCs). Additionally, CD24 induces drug resistance in various tumor cells following chemotherapy. To counteract the tumor-promoting effects of CD24, several treatment strategies targeting CD24 have been explored, such as the use of CD24 monoclonal antibodies (mAb) alone, the combination of CD24 and chemotoxic drugs, or the combination of these drugs with other targeted immunotherapeutic techniques. Regardless of the approach, targeting CD24 has demonstrated significant anti-tumor effects. Therefore, the present study focuses on anti-tumor therapy and provides a comprehensive review of the structure and fundamental physiological function of CD24 and its impact on tumor development, and suggests that targeting CD24 may represent an effective strategy for treating malignant tumors. [ABSTRACT FROM AUTHOR]

• Osteosarcoma is the most common malignant bone tumor in children and adolescents. • The tumor microenvironment releases substances that promote tumor cell metastasis. • The paper reviews research on osteosarcoma metastasis and the tumor microenvironment. Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. It is characterized by a rapid progression, poor prognosis, and early pulmonary metastasis. Over the past 30 years, approximately 85% of patients with osteosarcoma have experienced metastasis. The five-year survival of patients with lung metastasis during the early stages of treatment is less than 20%. The tumor microenvironment (TME) not only provides conditions for tumor cell growth but also releases a variety of substances that can promote the metastasis of tumor cells to other tissues and organs. Currently, there is limited research on the role of the TME in osteosarcoma metastasis. Therefore, to explore methods for regulating osteosarcoma metastasis, further investigations must be conducted from the perspective of the TME. This will help to identify new potential biomarkers for predicting osteosarcoma metastasis and assist in the discovery of new drugs that target regulatory mechanisms for clinical diagnosis and treatment. This paper reviews the research progress on the mechanism of osteosarcoma metastasis based on TME theory, which will provide guidance for the clinical treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

With the development of the social economy, unhealthy living habits and eating styles are gradually affecting people's health in recent years. As a chronic liver disease, NAFLD is deeply affected by unhealthy living habits and eating styles and has gradually become an increasingly serious public health problem. As a protein complex in clinical research, the inflammasomes play a crucial role in the development of NAFLD, atherosclerosis, and other diseases. This paper reviews the types, composition, characteristics of inflammasomes, and molecular mechanism of the inflammasome in NAFLD. Meanwhile, the paper reviews the drugs and non-drugs that target NLRP3 inflammasome in the treatment of NAFLD in the past decades. we also analyzed and summarized the related experimental models, mechanisms, and results of NAFLD. Although current therapeutic strategies for NAFLD are not effective, we expect that we will be able to find an appropriate treatment to address this problem in the future with further research on inflammasome. [ABSTRACT FROM AUTHOR]

• Ultrasound combined with tumor immunotherapy made encouraging new progress in both basic research and clinical treatment. • Ultrasound can increase the delivery of immunomodulatory substances and enhance the effect of immunotherapy. • Ultrasound can be used to improve the body's immune response to tumors. Immunotherapy has become a revolutionary method for treating tumors, offering new hope to cancer patients worldwide. Immunotherapy strategies such as checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and cancer vaccines have shown significant potential in clinical trials. Despite the promising results, there are still limitations that impede the overall effectiveness of immunotherapy; the response to immunotherapy is uneven, the response rate of patients is still low, and systemic immune toxicity accompanied with tumor cell immune evasion is common. Ultrasound technology has evolved rapidly in recent years and has become a significant player in tumor immunotherapy. The introductions of high intensity focused ultrasound and ultrasound-stimulated microbubbles have opened doors for new therapeutic strategies in the fight against tumor. This paper explores the revolutionary advancements of ultrasound combined with immunotherapy in this particular field. [ABSTRACT FROM AUTHOR]

• The new oral vaccine NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S was successfully developed. • NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S can activate host immunity. • NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S can protect the piglets against infection with PEDV. Porcine rotavirus (PoRV) poses a threat to the development of animal husbandry and human health, leading to substantial economic losses. VP6 protein is the most abundant component in virus particles and also the core structural protein of the virus. Firstly, this study developed an antibiotic-resistance-free, environmentally friendly expression vector, named asd-araC-PBAD-alr (AAPA). Then Recombinant Lactiplantibacillus plantarum (L. plantarum) strains induced by arabinose to express VP6 and VP6-pFc fusion proteins was constructed. Subsequently, This paper discovered that NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S could enhance host immunity and prevent rotavirus infection in neonatal mice and piglets. The novel recombinant L. plantarum strains constructed in this study can serve as oral vaccines to boost host immunity, offering a new strategy to prevent PoRV infection. [ABSTRACT FROM AUTHOR]

• E-MPBs shows sustained cellular uptake by microglia. • E-MPBs exhibits anti-ROS and anti-inflammation properties against M1 microglia. • E-MPBs develops a novel nanoplatform for SCI. Developing biomimetic nanoparticles without off-target side-effects remains a major challenge in spinal cord injury (SCI) immunotherapy. In this paper, we have conducted a drug carrier which is biocompatible macrophages-exocytosed exosome-biomimetic manganese (Mn)-iron prussian blue analogues (MPBs) for SCI immunotherapy. Exosome-sheathed MPBs (E-MPBs) exhibit promoted microglia accumulation, alleviation from H 2 O 2 -induced microenvironment and inhibition of apoptosis and inflammation in vitro. In addition, E-MPBs possessed significant tissue repair and neuroprotection in vivo. These properties endowed E-MPBs with great improvement in vivo in function recovery, resulting in anti-neuroinflammation activity and excellent biocompatibility in mice SCI model. As a promising treatment for efficient SCI immunotherapy, these results demonstrate the use of exosome-sheathed biomimetic nanoparticles exocytosed by anti-inflammation cells is feasible. [ABSTRACT FROM AUTHOR]

[Display omitted] • This paper constructs a novel vaccine that utilizes virus-like particles in combination with peptides to induce high titers of antibody production in vivo. • This vaccine inhibits the binding of interleukin-1 and its receptor by targeting the interleukin-1 receptor type I and inhibits the downstream signaling pathway. • This novel vaccine reduces the progression of atherosclerosis, maintains cardiac function after myocardial infarction and reduces inflammation levels in animals. • This immunotherapy drug will largely improve the way coronary atherosclerotic heart disease is treated and improve patient compliance. There is mounting evidence indicating that atherosclerosis represents a persistent inflammatory process, characterized by the presence of inflammation at various stages of the disease. Interleukin-1 (IL-1) precisely triggers inflammatory signaling pathways by binding to interleukin-1 receptor type I (IL-1R1). Inhibition of this signaling pathway contributes to the prevention of atherosclerosis and myocardial infarction. The objective of this research is to develop therapeutic vaccines targeting IL-1R1 as a preventive measure against atherosclerosis and myocardial infarction. ILRQβ-007 and ILRQβ-008 vaccines were screened, prepared and then used to immunize high-fat-diet fed ApoE-/- mice and C57BL/6J mice following myocardial infarction. Progression of atherosclerosis in ApoE-/- mice was assessed primarily by oil-red staining of the entire aorta and aortic root, as well as by detecting the extent of macrophage infiltration. The post-infarction cardiac function in C57BL/6J mice were evaluated using cardiac ultrasound and histological staining. ILRQβ-007 and ILRQβ-008 vaccines stimulated animals to produce high titers of antibodies that effectively inhibited the binding of interleukin-1β and interleukin-1α to IL-1R1. Both vaccines effectively reduced atherosclerotic plaque area, promoted plaque stabilization, decreased macrophage infiltration in plaques and influenced macrophage polarization, as well as decreasing levels of inflammatory factors in the aorta, serum, and ependymal fat in ApoE-/- mice. Furthermore, these vaccines dramatically improved cardiac function and macrophage infiltration in C57BL/6J mice following myocardial infarction. Notably, no significant immune-mediated damage was observed in immunized animals. The vaccines targeting the IL-1R1 would be a novel and promising treatment for the atherosclerosis and myocardial infarction. [ABSTRACT FROM AUTHOR]

• A discussion of research advances in the use of genetically engineered bacteria in conjunction with traditional modalities for the treatment of tumors, such as immunotherapy, chemotherapy, and radiation therapy. • An overview of common modifications of genetically engineered bacteria. • A discussion of the progress of clinical trials related to genetically engineered bacteria. Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy. [ABSTRACT FROM AUTHOR]

• Sepsis is the leading cause of death in ICU patients and an effective treatment is still lacking. Therefore, research in this area is necessary and of great value. • This review summarizes the latest findings and gaps related to the NLRP3 inflammasome, a key player in the innate immune system and the pathological process of sepsis. • Many studies suggested that targeting the NLRP3 inflammasome coule be applied to treat sepsis and sepsis-related organ dysfunction. Sepsis is the host immune imbalance following infection and leads to organ dysfunction, with highly complicated pathophysiology. To date, sepsis still lacks effective therapies with high mortality rates. Recently, numerous studies have highlighted the potential of NLRP3 inflammasome as a therapeutic target during sepsis. NLRP3 inflammasome is a protein complex that could induce the activation of caspase-1 and the following release of pro-inflammatory cytokines such as IL-1β and IL-18. It was demonstrated that NLRP3 inflammasome was involved in the development and progression of sepsis. In contrast, inhibition of NLRP3 inflammasome activation could mitigate the inflammatory response, protect organ function, and improve outcomes and mortality. This paper illustrated the activation pathways of the NLRP3 inflammasome and its possible molecular mechanisms in the pathophysiology of sepsis. Meanwhile, the beneficial effects of inhibiting NLRP3 activation in sepsis-related organ damage were also presented. In addition, the diverse role of NLRP3 inflammasome in bacterial clearance was addressed. Of note, several herbal extracts targeting NLRP3 inflammasome in the treatment of sepsis were emphasized. We hope that this paper could provide a basis for further drug research targeting NLRP3 inflammasome. [ABSTRACT FROM AUTHOR]

• In the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. • The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. • In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis. • The interference of toll-like receptors (TLRs) and its intracellular signaling pathway can regulate the liver inflammatory response and cirrhosis process. • Drug treatment of intestinal dysbiosis and TLRs activation may slow cirrhosis progression. • With the further study of intestinal microbiota and TLRs on the progression of cirrhosis, it offers a new way of preventing and treating inflammatory response and fibrosis diseases. Cirrhosis is a progressive chronic liver disease caused by one or more causes and characterized by diffuse fibrosis, pseudolobules, and regenerated nodules. Once progression to hepatic decompensation, the function of the liver and other organs is impaired and almost impossible to reverse and recover, which often results in hospitalization, impaired quality of life, and high mortality. However, in the early stage of cirrhosis, there seems to be a possibility of cirrhosis reversal. The development of cirrhosis is related to the intestinal microbiota and activation of toll-like receptors (TLRs) pathways, which could regulate cell proliferation, apoptosis, expression of the hepatomitogen epiregulin, and liver inflammation. Targeting regulation of intestinal microbiota and TLRs pathways could affect the occurrence and development of cirrhosis and its complications. In this paper, we first reviewed the dynamic change of intestinal microbiota and TLRs during cirrhosis progression. And further discussed the interaction between them and potential therapeutic targets to reverse early staged cirrhosis. [ABSTRACT FROM AUTHOR]

• Knockdown of IFIT3 represses M1 polarization. • IFIT3 does not affect IL-4 induced M2 polarization of microglia. • Knockdown of IFIT3 blocks the activation of STAT1 and NF-ĸB pathways. • IFIT3 regulates the polarization of microglia, thereby facilitating MS. The key to the treatment of multiple sclerosis (MS) is to promote the transition from inflammation-induced demyelination to remyelination. Polarization of microglia towards M1 or M2 phenotype is critical in this transition. Interferon induced protein with tetratricopeptide repeats 3 (IFIT3) is involved in inflammatory reaction and up-regulated in M1-polarized macrophages. However, its effect on microglia during MS has not been reported. In this paper, we demonstrated the important role of IFIT3 in selectively regulating microglia polarization. The expression of IFIT3 was increased when microglia were polarized towards M1, but did not change under M2 polarization. The knockdown of IFIT3 selectively inhibited M1 polarization, while M2 polarization was not affected by IFIT3 silencing. Furthermore, the activation of signal transducer and activator of transcription 1 (STAT1) and nuclear factor kappa-B (NF-ĸB) signaling in M1 polarized microglia was suppressed by downregulating IFIT3. In experimental autoimmune encephalitis (EAE) mice, an animal model of MS, IFIT3 expression was upregulated. The disease progression, inflammatory infiltration and demyelination in the EAE mice were alleviated by silencing IFIT3. The inhibitory effects of IFIT3 knockdown on M1 polarization and STAT1 and NF-ĸB pathways were also confirmed in the spinal cord of EAE mice. In summary, our findings suggest that IFIT3 selectively intensified microglia polarization towards the pro-inflammatory M1 phenotype, and may contribute to the progression of MS. [ABSTRACT FROM AUTHOR]

• Infection is an important cause of early death in multiple myeloma. • This study is the first to demonstrate a direct relationship between immunoparesis and early infection in multiple myeloma by using clinical data. • We established a new nomogram for predicting the early grade ≥ 3 infection in newly diagnosed multiple myeloma by using immunoparesis and other clinical indicators. • Our nomogram was composed of immunoparesis, BMPC, D-dimer, serum β2 microglobulin, albumin, and eGFR. Infection, a significant cause of death in multiple myeloma (MM) patients, is a common complication and is closely associated with immunoparesis. There exists no clear definition of early infection, so early infection is defined in this paper as the occurrence within 3 months after diagnosis, considering the high incidence of infections within 3 months after diagnosis. This study established a new nomogram model based on immunoparesis to identify MM patients with high-risk early infection. Methods: A retrospective collection of 430 NDMM patients from June 2013 to June 2022 was conducted, and the patients were further divided into a training cohort and a validation cohort. In the training cohort, the least absolute shrinkage and selection operator (LASSO) was used to select the best variables that can be used to establish a new nomogram prediction model. Validation was performed in the validation and entire cohorts. Results: After diagnosis, 67.7 % of the patients suffered from severe infection within 1 year, and 59.5 % experienced the first severe infection within 3 months. Variables associated with an increased risk of severe infection in the first 3 months included: BMPC, D-dimer, serum β2 microglobulin, immunoparesis, albumin, and eGFR. The nomogram based on the above six factors achieved a good C-index of 0.754, 0.73, and 0.731 in predicting early infection in the training cohort, validation cohort, and entire cohort, respectively. Finally, the time-dependent receiver operating characteristic (ROC) curve and decision curve analysis (DCA) of the nomogram showed that the model provided superior diagnostic capacity and clinical net benefit. Conclusion: In this study, we established a nomogram model to predict early grade ≥ 3 infection in NDMM patients. This model can assist clinicians in identifying NDMM patients with high-risk infections and improve their prognosis through early intervention. [ABSTRACT FROM AUTHOR]

Study on the constituents of bioactive culture broth extract (CBE) of Pseudomonas sp. (ABS-36) explored the secretion of an array of cyclic dipeptides (CDPs) and twenty of them had been isolated and reported in the present paper. Six major CDPs [(cyclo(Leu-Pro) (1), cyclo(Val-Pro) (2), cyclo(Leu-hydroxy-Pro) (9), cyclo(Pro-Tyr) (10), cyclo(Pro-Ala) (11) and cyclo(Gly-Pro) (12)] exhibited pan cytokine inhibition effect by inhibiting key pro-inflammatory cytokines IL-1β, TNF-α and IL-6 tested under various cell based assays. With this background, the effect of these six CDPs in treating renal inflammation was screened using crystal-induced nephropathy model in mice at 50 mg/kg body weight through oral administration. cis -Cyclo(Val-Pro) (2) exhibited 57% inhibition of plasma IL-1β protein expression and 35.2% inhibition of elevated blood urea nitrogen. Further, cis -cyclo(Val-Pro) (2) attenuated renal injury as demonstrated by significant reduction of mRNA expressions of IL-1β (P < 0.01) and kidney injury marker-1 (P < 0.001). Furthermore, evaluation of tubular-necrosis, -dilation and -cast in the histological sections exhibited moderate protection of renal tissues by cis -cyclo(Val-Pro) (2). All the tested CDPs reduced the nitrite production and were interestingly non-cytotoxic. • Culture broth extract (CBE) of Pseudomonas sp. (ABS-36) was found to inhibit pro-inflammatory cytokines. • Twenty cyclic dipeptides (CDPs) were isolated from CBE. Seventeen of them are reported for the first time from this source. • In-vitro studies explored pan cytokine inhibition effect (IL-1β, TNF-α and IL-6) of six proline-based CDPs • They were tested by crystal-induced nephropathy mice model to access renal anti-inflammation effect. • Cyclo(Val-Pro) attenuated renal injury by controlling the plasma IL-1β and BUN levels. [ABSTRACT FROM AUTHOR]

The classical renin-angiotensin system (RAS) is known to be a key regulator of blood pressure as well as fluid and electrolyte homeostasis. Additionally, it is now evident that components of the RAS are produced and act locally in many tissues, including liver, kidney, heart, lung, eye, bone, reproductive organ, adipose, and adrenal tissue, and these components are collectively known as tissue RAS. Recently, several studies have shown that local bone RAS is directly involved in bone metabolism, and activation of skeletal RAS plays an important role in bone diseases, such as osteoporosis, arthritis, and deterioration as well as in fracture healing. Based on the identification of RAS components in bone, we examined a new therapeutic approach to attenuate bone diseases through RAS inhibitors: renin inhibitor, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers. In this paper, we provide a systematic review of the skeletal RAS in the pathophysiology of bone diseases and the beneficial effect of RAS inhibitors on bone tissue. • The RAS in local bone tissue is directly involved in bone metabolism. • Activation of skeletal RAS plays an important role in osteoarticular diseases. • RAS inhibitors would be prospective candidates for treatment of osteoarticular diseases. [ABSTRACT FROM AUTHOR]

Paeonia suffruticosa possesses various medicinal benefits and has been used extensively in traditional oriental medicine for thousands of years. Paeonol is the main component isolated from the root bark of Paeonia suffruticosa. The pharmacological effects of Paeonia suffruticosa are mostly attributed to paeonol. Paeonol injection has been successfully applied in China for nearly 50 years for inflammation/pain-related indications. Currently, the dosage forms of paeonol approved by China Food and Drug Administration include tablet, injection, and external preparations such as ointment and adhesive plaster. So far, the clinical applications of paeonol are mainly focusing on the anti-inflammatory activity. Studies of other pharmacological activities of paeonol are developing rapidly, and which may play an important role in the future. Besides, substantial mechanisms of pharmacological action of paeonol have been clarified in recent years. In this review, we summarize the pharmacological effects anti-inflammatory, neuroprotective, anti-tumor, anti-cardiovascular diseases and associated mechanisms of action of paeonol up to date. • Pharmacological effects of paeonol are reviewed for the first time. • Pharmacological mechanisms of action of paeonol are reviewed up to date. • Paeonol derivatives are potentially attractive drugs worth to be studied further. [ABSTRACT FROM AUTHOR]

Abstract Multiple sclerosis is an autoimmune neurodegenerative disease, which usually caused by inflammation, demyelination, and axonal injury. The currently available medications for multiple sclerosis do not directly promote myelin sheath repair. Therefore, many researches have attempted to achieve better therapeutic effects through promoting remyelination. Natural products not only alleviate clinical symptoms, but also have the unique advantages of protecting and repairing effects on nervous system. We here present a systematic review on published papers about treating multiple sclerosis by natural products, aiming to provide comprehensive information on natural products in the treatment of multiple sclerosis. Highlights • Natural products (NPs) are effective in the treatment of multiple sclerosis (MS). • NPs inhibit inflammation and regulate the immune response in MS. • NPs protect the central nervous system in MS. • NPs repair damaged myelin sheath in MS. • Anti-MS mechanisms (anti-inflammatory, immune regulation, neuroprotection and nervous system repairing) of NPs are analyzed. [ABSTRACT FROM AUTHOR]

Abstract As antigen-presenting cells (APC), B cells exert a variety of immune regulatory functions mainly by presenting antigens, triggering immune response, and producing antibodies for immune regulation. Regulatory B cells (Bregs) are special subpopulations of B cells with immune-regulating or immune-suppressing properties and play a role in peripheral tolerance. Bregs suppress immune response through inhibiting the differentiation of dendritic cells (DCs), suppressing the proliferation of helper T1(TH1) cells and helper T17 (TH17) cells, inducing the differentiation of fork head transcription factor p3 positive regulatory T cells (FoxP3+ Tregs). Different subsets of Bregs have distinct phenotypes and markers. Different subsets of Bregs participate in immune modulation by different ways. The absence or loss of Bregs exacerbates the severity of many disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and graft-versus-host-disease (GVHD). Bregs are also involved in tumor immunosuppressive effect and inhibit the antitumor immune process. In this article, we review the research advances of Bregs in autoimmune diseases, GVHD and tumor. Highlights • Previous studies have shown that regulatory B cells play important roles in inflammatory diseases and tumor. • There is no systematic review of the role of regulatory B cells in inflammatory diseases and tumor. • In this paper, the role of regulatory B cells in inflammatory diseases and tumors is systematically reviewed. • This article provides researchers with the latest systematic research of regulatory B cells. [ABSTRACT FROM AUTHOR]

Abstract: This paper investigates how BST204, a fermented ginseng extract, affects the expression and mechanism of cyclooxygenase-2 (COX-2). BST204 was prepared by incubating crude ginseng extract with ginsenoside-β-glucosidase. Unexpectedly, BST204 had no effect on the level of COX-2 protein in unstimulated RAW 264.7 cells, and it suppressed the level of COX-2 protein and PGE2 production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It did not show any suppressive effect, though, on the COX-2 mRNA level. To investigate the suppressive mechanism of COX-2 protein, the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, were measured. The phosphorylation of p70 S6 kinase, not 4E-BP1, was increased by LPS in a time-dependent manner, and was inhibited by BST204 in a dose-dependent manner. The expression of COX-2 protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of COX-2 protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation. [Copyright &y& Elsevier]

• This paper compares and analyzes the difference of immune status of T lymphocytes and their subsets in hepatitis B patients under different ALT conditions for the first time. • For the first time, this paper reveals the changes of immune status and the effects of antiviral therapy on immune function when ALT is greater than or equal to 2 times the normal upper limit. • This paper puts forward for the first time the significance of using ALT as a node to judge the immune function of the body. The aim of the present study was to explore the effect of hepatitis B virus on T lymphocyte and its subsets in different ALT states, and elucidate the immunological mechanism of ALT basing antiviral therapy for hepatitis B. 363 chronic hepatitis B patients were selected as the study subjects. According to ALT abnormalities, the patients were divided into three study groups. ALT normal group 131 cases, normal≦ ALT < 2 times of upper limit group 110 cases, ALT ≥ 2 times of upper limit group 122 cases. Entecavir was given to the ALT ≥ 2 times of upper limit group patients and followed up for 24 weeks. The hepatitis B antigen antibody parameters were measured by chemiluminescence immunoassay analyzer, the liver function parameters were measured by automatic biochemical analyzer, the hepatitis B virus load were measured by quantitative PCR analyzer, T lymphocytes were detected by flow cytometry, the level of IL-2, IFN-γ, IL-4 and IL-10 were detected by enzyme-linked immunosorbent assay. Detecting the influence of different hepatitis B viru loads in different groups on immunological indexes, and the virological and immunological indexes changes in before and after antiviral therapy patients. In the ALT normal group, different virus load hepatitis B virus had minor effect on T lymphocytes and their subsets (P > 0.05). In the ALT ≥ double upper limit of normal group. with the virus load increased, The total number of T lymphocytes, CD3+ CD4 + T lymphocytes decreased, (P < 0.05)CD3+ CD8 + T lymphocytes increased(P < 0.05). With the virus load increased the cytokines IL-2, IFN-γ which reflect the Th1 lymphocytes increased(P < 0.05), the cytokines IL-4、IL-10 which reflect the Th2 lymphocytes decreased(P < 0.05). Before and after 24 weeks of entecavir treatment, the patient's HBV-DNA decreased significantly(P < 0.05) and the body's immune function improved significantly. (P < 0.05)The influence of hepatitis B virus on immune function is different in different ALT states. Therefore, the scientific significance of ALT grouping in the hepatitis B treatment can be clarified from the immunological point. [ABSTRACT FROM AUTHOR]

Abstract Development of active compounds to control inflammation against systemic inflammatory response syndrome (SIRS) is critical important. Dioscin shows anti-inflammatory effects in our previous works. However, the action of the compound on SIRS still remained unknown. In the present paper, zymosan induced generalized inflammation (ZIGI) models in mice and rats, and PMA-differentiated THP‑1 cells stimulated by lipopolysaccharide (LPS) and Pam3-Cys-Ser-Lys4 (Pam3CSK4) were used. The results showed that dioscin significantly inhibited the proliferation of THP‑1 cells stimulated by LPS and Pam3CSK4, obviously reduced the soakage of inflammatory cells and necrosis in liver, kidney and intestine of rats and mice, and reduced peritoneal ascites fluid compared with ZIGI model groups. In addition, dioscin significantly declined the levels of alanine transaminase (ALT), aspartate transaminase (AST), creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA) and myeloperoxidase (MPO), increased the levels of superoxide dismutase (SOD) in rats and mice. The migration of macrophages in tissues was also suppressed by dioscin. Mechanism investigation showed that dioscin significantly inhibited the expression levels of TLR2, MyD88, NF‑κb, HMGB‑1, increased the expression levels of IKBα, and decreased the mRNA levels of interleukin‑1 beta (IL‑1β), interleukin‑6 (IL‑6) and tumor necrosis factor‑alpha (TNF‑α) in liver, kidney, intestine tissues of rats and mice, and in PMA-differentiated THP‑1 cells, which were further confirmed by TLR2 siRNA silencing in vitro. In conclusion, our data confirmed that dioscin exhibited protective effects against SIRS via adjusting TLR2/MyD88 signal pathway, which should be developed as one potent candidate to treat SIRS in the future. Graphical abstract Unlabelled Image Highlights • Dioscin significantly inhibited the proliferation of THP‑1 cells stimulated by LPS. • Dioscin showed protective effects against SIRS in mice and rats. • Dioscin suppressed the migration of macrophages in tissues of rats and mice. • Dioscin adjusted TLR2/MyD88 pathway in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Abstract Neurodegenerative diseases are closely related to neuroinflammation. Drugs targeting inflammation have been proved to be effective in many animal models. Salvianolic acid C (SalC) is a compound isolated from Salvia miltiorrhiza Bunge, a plant with reported effects of inhibiting inflammation. However, the anti-inflammation effects and biological mechanisms of SalC on LPS-stimulated neuroinflammation remain unknown. The aim of this paper was to study its protective effects and its anti-inflammation mechanisms. LPS was used both in vivo and in vitro to induce neuroinflammation in SD rats and microglia cells. MTT assay was carried out to detect cell viability. The levels of TNF‑α, IL‑1β, IL‑6, IL‑10 and PGE 2 were detected by ELISA method. The expressions of p‑AMPK, p‑NF‑κB p65, p‑IκBα, Nrf2, HO‑1 and NQO1 proteins were examined by Western blot analysis. The nuclear translocation of NF‑κB p65 was studied by immunofluorescence assay. The specific Nrf2 siRNA was used to clarify the interaction between Nrf2 and NF‑κB p65. The AMPK inhibitor Compound C was used study the upstream protein of Nrf2. Results showed that LPS induced the overexpression of inflammatory cytokines and mediated the phosphorylation and nuclear translocation of NF‑κB p65 in rat brains and microglia cells. SalC reversed the inflammatory response induced by LPS and inhibited the NF‑κB activation. SalC also upregulated the expression of p‑AMPK, Nrf2, HO‑1 and NQO1. But the anti-inflammation and NF‑κB inhibition effects of SalC were attenuated by transfection with specific Nrf2 siRNA or interference with the potent AMPK inhibitor Compound C. In conclusion, SalC inhibited LPS-induced inflammatory response and NF‑κB activation through the activation of AMPK/Nrf2 signaling both in vivo and in vitro. Graphical abstract Unlabelled Image Highlights • Salvianolic acid C inhibited LPS-induced NF‑κB activation. • Salvianolic acid C upregulated the levels of p‑AMPK, Nrf2, HO‑1 and NQO1 proteins. • The activation of AMPK/Nrf2 attenuated NF‑κB mediated inflammatory response. [ABSTRACT FROM AUTHOR]

Sepsis is characterized by the extensive release of cytokines and other mediators. It results in a dysregulated immune response and can lead to organ damage and death. Curcumin has anti-inflammatory properties and immunoregulation functions in various disorders such as sepsis, cancer, rheumatoid arthritis, cardiovascular diseases, lung fibrosis, gallstone formation, and diabetes. This paper investigates the effects of curcumin on immune status and inflammatory response in mice subjected to cecal ligation and puncture (CLP). Inflammatory tissue injury was evaluated by histological observation. Magnetic microbeads were used to isolate splenic CD4 + CD25 + regulatory T cells (Tregs), and phenotypes were then analyzed by flow cytometry. The levels of Foxp3 were detected by Western blot and real-time PCR and cytokine levels were determined by enzyme-linked immunosorbent assay. We found that the administration of curcumin significantly alleviated inflammatory injury of the lung and kidney in septic mice. The suppressive function of Treg cells was enhanced and the plasma levels of IL-10 increased after treatment with curcumin. Furthermore, the secretion of plasma TNF-α and IL-6 was notably inhibited in septic mice treated with curcumin and administration with curcumin could improve survival after CLP. These data suggest that curcumin could be used as a potential therapeutic agent for sepsis. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the effect of glabridin (Glab) on psoriasis. We observed that Glab significantly suppressed the levels of nitric oxide (NO), NF-κB subunit p65, interleukin (IL)-6, and IL-1β in lipopolysaccharide (LPS)-stimulated HaCaT cells. In addition, Glab treatment reduced the expression of IL-17A, IL-22, and IL-23 in TNF- α- stimulated-HaCaT cells. These findings prompted us to test whether Glab could be used to treat psoriasis in vivo. The effects of Glab on PASI scores, histopathological changes, oxidative/anti-oxidative indexes and pro-inflammatory cytokines in IMQ-induced mice were investigated. The results indicated that Glab could reduce the PASI scores and ameliorate the deteriorating histopathology. Interestingly, RT-PCR revealed that Glab significantly decreased the mRNA expression of p65, IL-6, IL-1β, IL-17A, IL-22, and IL-23. These results were confirmed by Western blot analysis and immunohistochemistry staining. In conclusion, our present study revealed that Glab had beneficial effects on psoriasis, and the underlying mechanism may be associated with the downregulation of pro-inflammatory cytokines and the improvement of antioxidant status. Hence, Glab is a promising candidate molecule for development of effective psoriasis therapies. [ABSTRACT FROM AUTHOR]