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Objective To explore the role of MAPK4 in cervical squamous cell carcinoma (CSCC) for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets. Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis. Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis. A nomogram was constructed based on MAPK4 mRNA levels. Western blot, CCK-8, colony formation, and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC. DIA proteome sequencing was used to identify effector molecules regulated by MAPK4. Combined with the above cell function experiments, the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression. Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis. The constructed nomogram based on MAPK4 can accurately predict the 1-, 3-, and 5-year survival rates of patients. Compared with that in normal cervical tissues, MAPK4 protein expression was up-regulated in tumors. MAPK4 knockdown substantially inhibited the proliferation, colony formation, migration, and invasion of CSCC ME180 and SiHa cells. SLC3A2 is a downstream effector molecule of MAPK4 Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation, colony formation, migration, and invasion. Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC. MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression, making it a potential molecular therapeutic target for patients with CSCC [ABSTRACT FROM AUTHOR]

Objective To analyze the role of APEX family in hepatocellular carcinoma (HCC). Methods After expression data of HCC and normal liver tissues from public databases (TCGA and TNM plot) were collected, the expression patterns, functional networks, and potential biological pathways of the APEX family in HCC were investigated through differential expression analysis, construction of protein-protein interaction networks(PPI), and Gene Set Enrichment Analysis (GSEA). Receiver operating characteristic (ROC) curve analysis was used to assess the potential of APEX family members as diagnostic markers for HCC, and their correlation with HCC prognosis was anlyzed through survival analysis. RT-qPCR and Western blotting we performed to detect the expression of APEX1 and APEX2 at mRNA and protein levels in liver cells and HCC cells. The effect of silencing APEX1 and APEX2 in HCC cells were determined through CCK-8 assay, EdU assay, scratch healing test, and Transwell assay. Results The expression levels of the 2 members of the APEX family, APEX1 and APEX2, were significantly higher in the HCC samples than the normal liver tissues (P < 0.01). The results of ROC curve analysis on public databases showed that the AUC value of APEX1 and APEX2 in predicting HCC was 0.922 and 0.917, respectively. PPI network analysis revealed that APEX family members regulated cell cycle through various signaling pathways. Survival analysis indicated that HCC patients with high expression levels of APEX1 and APEX2 had significantly shorter overall survival than those with low levels (P < 0.05), and APEX1 and APEX2 were highly correlated with traditional tumor survival prognostic factors Ki-67 and TP53 (P < 0.001). The mRNA and protein levels of APEX1 and APEX2 were significantly higher in the liver cancer cells than the normal liver cells (P < 0.05). In addition, silencing APEX1 and APEX2 resulted in notably reduced proliferation, migration, and invasion abilities of HCC cells (P < 0.05). Conclusion APEX1 and APEX2 can serve as potential biomarkers for HCC diagnosis and prognosis assessment, and their involvement in the regulation of HCC proliferation and metastasis provides new strategies and targets for the early diagnosis and individualized treatment of HCC.

ObjectiveTo explore the role of MAPK4 in cervical squamous cell carcinoma (CSCC) for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets. MethodsThe TCGA cohort was subjected to Kaplan-Meier survival analysis. Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis. A nomogram was constructed based on MAPK4 mRNA levels. Western blot, CCK-8, colony formation, and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC. DIA proteome sequencing was used to identify effector molecules regulated by MAPK4. Combined with the above cell function experiments, the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression. ResultsCSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis. The constructed nomogram based on MAPK4 can accurately predict the 1-, 3-, and 5-year survival rates of patients. Compared with that in normal cervical tissues, MAPK4 protein expression was up-regulated in tumors. MAPK4 knockdown substantially inhibited the proliferation, colony formation, migration, and invasion of CSCC ME180 and SiHa cells. SLC3A2 is a downstream effector molecule of MAPK4. Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation, colony formation, migration, and invasion. ConclusionMAPK4 is a candidate prognostic biomarker for patients with CSCC. MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression, making it a potential molecular therapeutic target for patients with CSCC.

Vitiligo is a chronic autoimmune disease characterized by depigmentation of the skin, significantly impacting patients' quality of life. Recent advances in immunological and molecular biological studies have identified numerous potential therapeutic targets for vitiligo, paving the way for novel treatment strategies. This article reviews the advancements in researching novel immunotherapy targets such as the JAK/ STAT pathway, PDE-4, Wnt/β-catenin pathway, and IL-15, along with their respective targeted drugs. The article aims to provide insights into the clinical translation of future therapeutic targets for vitiligo.

Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor, which is characterized by high mortality, easy metastasis and recurrence, low 5-year survival rate and poor clinical prognosis. At present, there are few treatments that directly target tumor cells. The most effective treatment for HCC is targeting the tumor immune microenvironment. Tumor cells are characterized by metabolic abnormalities to meet the high energy and biosynthesis needs associated with rapid tumor growth. With the deepening of research, it has been found that cholesterol is usually enriched in the tumor microenvironment, and liver cholesterol metabolism is involved in the occurrence and development of HCC. Therefore, exploring the molecular regulation process of cholesterol metabolism in the liver, elucidating the role of cholesterol in HCC, and seeking potential targets for the treatment of HCC is one of the important scientific research issues that have attracted much attention. This article briefly reviews the role of cholesterol in HCC and its potential therapeutic value, and provides strong evidence for further research and in-depth discussion of the relationship between cholesterol and HCC. [ABSTRACT FROM AUTHOR]

Numerous studies have confirmed that Alzheimer's disease is a disorder related to dysfunction of blood brain barrier (BBB). How to improve the physiological function of BBB by restoring its structural integrity, and then improve the outcome and prognosis of AD will certainly bring new perspectives and opportunities for the prevention and treatment of this chronic disease. In this article, we review the research progress on AD from three aspects including the structural and functional changes of BBB and its pathogenesis, biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

Primary biliary cholangitis （PBC） is a disease with unclear etiology and pathogenesis. In recent years，it has become a hot topic to identify the potential pathogenesis and therapeutic targets of PBC by studying the changes of metabolic substances in PBC patients. Metabonomics are employed to comprehensively analyze the metabolic spectrum of PBC patients through mass spectrometry and nuclear magnetic resonance technology，providing assistance for the diagnosis and treatment of PBC. In this article，recent research progress upon metabonomics in PBC was reviewed，aiming to provide new ideas for clinical diagnosis and treatment of PBC.

Primary biliary cholangitis (PBC) is a disease with unclear etiology and pathogenesis. In recent years, it has become a hot topic to identify the potential pathogenesis and therapeutic targets of PBC by studying the changes of metabolic substances in PBC patients. Metabonomics are employed to comprehensively analyze the metabolic spectrum of PBC patients through mass spectrometry and nuclear magnetic resonance technology， providing assistance for the diagnosis and treatment of PBC. In this article, recent research progress upon metabonomics in PBC was reviewed, aiming to provide new ideas for clinical diagnosis and treatment of PBC. [ABSTRACT FROM AUTHOR]

The gut microbiota, also known as the second-largest gene pool in the body, is also increasingly identified as playing an important role in bone health. Although the natural physiological process of bone remodeling and the pathogenesis of bone resorption are well understood, the relationship between intestinal flora and bone metabolism is still not fully understood. The gut-bone axis can be used to clarify the relationship and influence of intestinal flora on bone metabolism. According to existing studies, the mechanism of intestinal microflora regulating bone health is mainly discussed from the aspects of microflora and nutrient metabolites, immune regulation, intestinal mucosal barrier, and endocrine regulation. This paper aims to summarize the research progress of gut microbiota in bone metabolism and provides theoretical reference for the treatment of some orthopedic diseases based on gut microbiota. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is the third leading cause of cancer mortality in the world. Unfortunately,traditional treatments have limited efficacy. Recent research shows that CAR-T immunotherapy is a promisingtreatment for GC. Using genetically engineered T cells designed to target a tumor specific antigen, researchersare able to harness the natural anti-tumor activity of T cells. Therefore, it is essential to choose specificantigens that are highly expressed on tumor cells but not on healthy cells. In this review, we present anoverview of the most important antigens for CAR-T therapy in the context of GC. A number of clinical studiespoint to the following as important markers: NKG2D, EpCAM, CLDN, MSLN, FOLR1, HER2, MUC1.Although these markers have been met with some success, the search for new and improved targets continues.

Oral lichen planus (OLP) is a chronic inflammatory disease of the mucosa, some of which will develop into oral squamous cell carcinoma (OSCC). However, the pathogenesis of OLP remains unknown, but autoimmunity has been suggested as a potential cause. MicroRNAs (miRNAs), which are small noncoding RNAs, have been reported to be involved in a series of physiological events as well as the progression of diseases. The evidence indicates that miRNAs may be highly related to both the initiation and malignant progression of OLP. MiR-146a, miR-26b, miR-155, miR-19a and miR-125a are able to trigger OLP by regulating autoimmunity, and miR-137, miR-125b, and miR-27b may accelerate the carcinogenesis of OLP. These miRNAs may be potential targets for prognosis and treatment. Subsequent studies are expected to focus on a more comprehensive exploration of the role of miRNAs in OLP (including specific action pathways and other OLP-related miRNAs), as well as the potential for miRNAs to predict the treatment outcome of OLP. This review provides an updated summary of the roles of miRNAs in OLP to provide new ideas and approaches to OLP research.

Novel drug discovery from the active ingredients of traditional Chinese medicine is the most distinctive feature and advantageous field of China, which has provided an unprecedented opportunity. However, there are still problems such as unclear functional substance basis, action targets and mechanism, which greatly hinder the clinical transformation of active ingredients in traditional Chinese medicine. Based on the analysis of the current status and progress of innovative drug research and development in China, this paper aimed to explore the prospect and difficulties of the development of natural active ingredients from traditional Chinese medicine, and to explore the efficient discovery of trace active ingredients in traditional Chinese medicine, and obtain drug candidates with novel chemical structure, unique target/mechanism and independent intellectual property rights, in order to provide a new strategy and a new model for the development of natural medicine with Chinese characteristics.

In the development of ovarian cancer, the aberrant lipid metabolism plays a critical role. Lysophosphatidic acid (LPA), a bioactive molecular, can bind to different G protein-coupled receptors and stimulate the proliferation, metastasis and invasion of ovarian cancer. On one hand, LPA could stimulate proliferation by promoting angiogenesis, regulating cell cycle, inhibiting apoptosis, promoting glucose metabolism and maintaining cancer stem cell (CSC) characteristics. On the other hand, LPA could stimulate the metastasis and invasion by enhancing the expression of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA), interfering intercellular junctions and cytoskeletons and inducing epithelialmesenchymal transition (EMT). What's more, testing plasma level of LPA alone or combining with other tumor biomarkers is more sensitive and specific. In this article, we review the latest knowledge on the molecular mechanism of LPA in the proliferation, migration and invasion of ovarian cancer as well as potential biological targets. [ABSTRACT FROM AUTHOR]

With the development of our society，the improvement of living standard，and the arrival of the era of population aging， the incidence of osteoporosis increases year by year and gradually becomes one of the chronic diseases that affect people's live． At present，however，traditional anti-osteoporosis drugs can not reduce fracture risk of this disease，and can not effectively improve bone mineral density as well as relieve pain and discomfort． With the further exploration of the pathogenesis of osteoporosis，signal pathways such as OPG/RANKL/RANK，Wnt，sclerostin as well as cathepsin K，have been discovered in the development of the osteoporosis，which may be the novel therapeutic targets of osteoporosis in the future． [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is one of the most common malignant tumors worldwide, and most of the patients are diagnosed at the advanced stage. Most of the treating options are comprehensive treatment, in which immunotherapy plays more and more important role. Melanoma antigen-associated gene-A (MAGE-A) family is a kind of cancer testis antigens. Except in germ cells of testis and trophoblast cells of placenta, MAGE-A family is highly expressed in cancerous tissues and participates in a variety of biological processes, such as cancer cell proliferation, differentiation and metastasis. In addition, cancer testis antigen also possesses good immunogenicity, which can induce humoral and cellular immune responses, is a good target for immunotherapy, and has good application value in the diagnosis, treatment and prognosis of GC. A variety of targeted therapeutic drugs based on MAGE-A are in phase I or II clinical trials, it has good safety and potential clinical application value. With the continuous progress of clinical trials and basic research on MAGE-A targets in GC, it is expected to provide a theoretical basis for clinical transformation and immunotherapy of MAGE-A in the future.

Alcoholic liver disease (ALD) is a leading cause of chronic liver disease worldwide; however, the pathogenesis of ALD is not fully understood and there are no targeted therapies for ALD. In this review article, we summarize the findings from recent studies that have characterized the pathogenesis and diagnosis of ALD. Several novel therapeutic targets for alcoholic hepatitis are also discussed. There is an urgent need to translate these targets into therapies for patients with ALD. [ABSTRACT FROM AUTHOR]

Vestibular schwannoma (VS) is one of the most common types of benign tumors of the central nervous system. At present, the prevailing treatment methods of VS include surgery, stereotactic radiotherapy, and follow-up observation, etc. However, there is still no drug therapy available for treating VS. Although the surgical technique is relatively mature, the complications cannot be completely avoided. Furthermore, both the growth rate of different cases and patients' sensitivity to radiotherapy vary greatly. With the constant progress made in molecular biology research, most of the studies on the growth mechanism of VS focus on the upstream and downstream of neurofibromin 2 ( NF 2) gene and merlin protein, and a number of corresponding targets, including receptor protein tyrosine kinase (RTK), vascular endothelial growth factor receptor (VEGFR), mammalian target of rapamycin complex 1 (mTORC1) and platelet derived growth factor receptor (PDGFR). It has been reported in some studies that quite a few drugs could inhibit the proliferation of VS cells. Most of the studies are still in the stage of in vitro cell experiment and/or animal experiment. A small number of studies have entered phase Ⅰ and phase Ⅱ clinical trials, but have not led to any clinical treatment yet. This paper provides a comprehensive understanding of the current status and the prospects of drug therapies of VS, which is conducive to the development of subsequent research., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Systemic lupus erythematosus (SLE) is a chronic and autoimmunity-mediated diffuse connective tissue disease. The mainstay of treatments for SLE mainly relies on corticosteroids and immunosuppressants, which have a series of unavoidable side effects. Therefore, it is of fundamental importance to search novel therapeutic targets for better treatment with favorable efficacy and minor side effects. Recent studies shed light on potential therapeutic targets for SLE, mainly covering the followings: B-cell/plasmocyte-related targets [B cell activating factor (BAFF), a proliferation-inducing ligand (APRIL), CD20, CD22, CD19/FcγRIIb, Bruton tyrosine kinase (Btk), and proteasome], T cell-related targets [calcineurin, mammalian target of rapamycin (mTOR), regulatory factor X1 (RFX1), and Rho kinase], macrophage-related targets (macrophage migration inhibitory factor), intracellular signaling molecules, cytokines (cereblon, histone deacetylase 6, Janus activated kinase/signal transducer and activator of transcription), co-stimulating factors (CD28/B7, CD40/CD154), IgE autoantibody, and gut microbiome. Among them, belimumab (a humanized monoclonal antibody against B-lymphocyte stimulator) and telitacicept (a recombinant human B-lymphocyte stimulator receptor-antibody fusion protein) have been sequentially approved for the clinical treatment of SLE in China. A variety of new targeted-therapy drugs are in the Phase 2 or Phase 3 clinical trials,among which anifrolumab (a human monoclonal antibody against type I interferon receptor subunit 1) has completed a Phase 3 clinical trial with good responses achieved, although its incidence of herpes zoster is higher than that in the control group. The research progress in both molecular mechanisms and new drug development for different therapeutic targets have greatly promoted our better and in-depth understanding of the pathogenesis of SLE, and have also reflected the complexity and heterogeneity of the disease. Successful development and clinical application of more novel therapies would no doubt usher in a new era of individualized treatment for SLE in the future.

Objective: To investigate differentially expressed genes associated with liver cancer using bioinformatics methods, and to screen out molecular markers for early diagnosis of liver cancer and potential molecular targets for immunotherapy. Methods: The microarray data associated with liver cancer were downloaded from Gene Expression Omnibus. JMP software was used for correlation analysis of GSE datasets, Limma program in R language was used to screen out differentially expressed genes, and the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis were performed for differentially expressed genes. A protein-protein interaction (PPI) network was also established for analysis. An analysis of specific expression associated with liver cancer was performed with reference to RNA-seq transcriptome data for other tumors obtained from TCGA to further identify specific differentially expressed genes in liver cancer, and a survival curve analysis was performed for patients with liver cancer. Results: A total of 92 differentially expressed genes were identified, with 21 upregulated genes and 71 downregulated genes. Through the GO, KEGG, and PPI analyses, RNA-seq data verified that only glypican 3 (GPC3) was upregulated in liver cancer, and MBL2, SDS, SLCO1B3, TDO2, SAA4, and SPP2 were downregulated. Conclusions: GPC3 might act as a target for immunotherapy, and other molecular markers may become molecular markers for early detection of liver cancer and potential targets for immunotherapy.

Nonalcoholic fatty liver disease(NAFLD) is a kind of metabolic liver injury, which is closely associated with insulin resistance and genetic susceptibility. Traditional Chinese herbs used in the treatment of nonalcoholic fatty liver disease are widely investigated in recent years. A series of recent studies show that the effects of the active components in traditional Chinese herbs on NAFLD are associated with activating AMPK signaling pathway, improving insulin resistance, modulating the activity and expression of peroxisome proliferator-activated receptor γ, antioxidant and anti-inflammatory activities and regulating intestinal flora. In this review, the potential therapeutic targets of the active components from traditional Chinese herbs for NAFLD would be summarized to provide a new thought for further research and clinical treatment of nonalcoholic fatty liver disease., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)