Endometriosis (EM), also known as Zhengjia in traditional Chinese medicine, is a common disease that significantly impacts women's health. An integrated treatment approach combining traditional Chinese medicine (TCM) and western medicine has demonstrated significant clinical efficacy in the management of this condition. Specifically, it has been effective in addressing blood circulation and other diseases. MicroRNAs (miRNAs), which are molecules important in gene regulation, have been implicated in various physiologic and pathologic processes. In this review, we systematically summarized the potential mechanisms underlying the integrated EM treatment, with a focus on the role of microRNAs (miRNAs). Current research suggests that integrated TCM and western medicine treatment may exert their therapeutic effects on EM by influencing the expression of miRNAs. Through miRNA modulation, such a treatment approach may inhibit the growth of ectopic lesions and alleviate clinical symptoms. This review will shed light on the specific miRNAs that have been implicated in the integrated treatment of EM, as well as their potential mechanisms of action. By consolidating the existing evidence, we aim to provide clinicians and researchers with a clearer understanding of the therapeutic benefits of the integrated approach and potentially identify new avenues for improving clinical treatment outcomes. Ultimately, this review will contribute to the growing body of knowledge in this field, providing a basis for further research and the development of more targeted and efficient treatment strategies for EM.

Seventy percent of breast cancer patients have an active estrogen receptor. Tamoxifen interferes with estrogen's ability to bind to cancer cells. The most challenging aspect of tamoxifen, however, is that breast cancer cells become resistant to its effects. Some studies have shown that alterations in miRNA expression contribute significantly to drug resistance in breast cancer. Therefore, the present systematic review aims to investigate miRNAs that significantly influence the response to tamoxifen treatment. The present study follows the PRISMA instructions. The Web of Science, PubMed, and Scopus databases were searched to retrieve English articles. The searches were conducted up to September 11, 2022. The search strategy included the terms "Tamoxifen", "Breast Neoplasm", and "MicroRNA". The inclusion criteria of this study are English, original, and experimental studies investigating miRNAs that are effective in the treatment efficacy of tamoxifen. A total of 565 articles were retrieved. After screening, 75 studies met our inclusion criteria. This systematic review study examined 105 miRNAs, of which 44 have a positive effect, and 47 miRNAs inhibit tamoxifen function. Fourteen miRNAs have a controversial effect, ie, some studies show positive and negative effects. The study of miRNAs affecting tamoxifen function in breast cancer patients may facilitate the identification of individuals at higher risk of disease recurrence. Conversely, it can potentially utilize appropriate interventions to defeat drug resistance effectively.

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.

Betel quid and areca nut are complex mixture carcinogens, but little is known about whether their derived single-agent arecoline or arecoline N-oxide (ANO) is carcinogenic, and the underlying mechanisms remain unclear. In this systematic review, we analyzed recent studies on the roles of arecoline and ANO in cancer and strategies to block carcinogenesis. In the oral cavity, flavin-containing monooxygenase 3 oxidizes arecoline to ANO, and both alkaloids conjugate with N-acetylcysteine to form mercapturic acid compounds, which are excreted in urine, reducing arecoline and ANO toxicity. However, detoxification may not be complete. Arecoline and ANO upregulated protein expression in oral cancer tissue from areca nut users compared to expression levels in adjacent normal tissue, suggesting a causal relationship between these compounds and oral cancer. Sublingual fibrosis, hyperplasia, and oral leukoplakia were diagnosed in mice subjected to oral mucosal smearing of ANO. ANO is more cytotoxic and genotoxic than arecoline. During carcinogenesis and metastasis, these compounds increase the expression of epithelial-mesenchymal transition (EMT) inducers such as reactive oxygen species, transforming growth factor-β1, Notch receptor-1, and inflammatory cytokines, and they activate EMT-related proteins. Arecoline-induced epigenetic markers such as sirtuin-1 hypermethylation, low protein expression of miR-22, and miR-886-3-p accelerate oral cancer progression. Antioxidants and targeted inhibitors of the EMT inducers used reduce the risk of oral cancer development and progression. Our review findings substantiate the association of arecoline and ANO with oral cancer. Both of these single compounds are likely carcinogenic to humans, and their mechanisms and pathways of carcinogenesis are useful indicators for cancer therapy and prognosis.

Antipsychotics represent the mainstay of schizophrenia pharmacological therapy, and their role has been expanded in the last years to mood disorders treatment. Although introduced in 1952, many years of research were required before an accurate picture of how antipsychotics work began to emerge. Despite the well-recognized characterization of antipsychotics in typical and atypical based on their liability to induce motor adverse events, their main action at dopamine D2R to elicit the "anti-psychotic" effect, as well as the multimodal action at other classes of receptors, their effects on intracellular mechanisms starting with receptor occupancy is still not completely understood. Significant lines of evidence converge on the impact of these compounds on multiple molecular signaling pathways implicated in the regulation of early genes and growth factors, dendritic spine shape, brain inflammation, and immune response, tuning overall the function and architecture of the synapse. Here we present, based on PRISMA approach, a comprehensive and systematic review of the above mechanisms under a translational perspective to disentangle those intracellular actions and signaling that may underline clinically relevant effects and represent potential targets for further innovative strategies in antipsychotic therapy.

A serotonergic dysfunction has been largely postulated as the main cause of depression, mainly due to its effective response to drugs that increase the serotonergic tone, still currently the first therapeutic line in this mood disorder. However, other dysfunctional pathomechanisms are likely involved in the disorder, and this may in part explain why some individuals with depression are resistant to serotonergic therapies. Among these, emerging evidence suggests a role for the astrocytic inward rectifier potassium channel 4.1 (Kir4.1) as an important modulator of neuronal excitability and glutamate metabolism. To discuss the relationship between Kir4.1 dysfunction and depression, a systematic review was performed according to the PRISMA statement. Searches were conducted across PubMed, Scopus, and Web of Science by two independent reviewers. Twelve studies met the inclusion criteria, analyzing Kir4.1 relationships with depression, through in vitro, in vivo, and post-mortem investigations. Increasing, yet not conclusive, evidence suggests a potential pathogenic role for Kir4.1 upregulation in depression. However, the actual contribution in the diverse subtypes of the disorder and in the comorbid conditions, for example, the epilepsy-depression comorbidity, remain elusive. Further studies are needed to better define the clinical phenotype associated with Kir4.1 dysfunction in humans and the molecular mechanisms by which it contributes to depression and implications for future treatments.

Silent information regulator 1 (Sirt1) involved in histone stability, transcriptional activity, and translocation. This systematic review aimed to summarize the effects of Resveratrol on Sirt1 expression.

Melphalan is a bifunctional alkylating agent that elicits its cytotoxic activity by rapidly forming an initial DNA monoadduct, which then produces an inter-strand crosslink. Most studies exploring the role of inherited differences in DNA repair and melphalan outcomes focus on inter-strand crosslink repair, however, monoadduct repair likely plays a key role since it minimises the ultimate production of these crosslinks. The purpose of this systematic review was to assess evidence of an association between variation in monoadduct repair pathways and melphalan response.

Curcumin is a bioactive ingredient found in the Rhizomes of Curcuma longa. Curcumin is well known for its chemopreventive and anti-cancer properties. Recent findings have demonstrated several pharmacological and biological impacts of curcumin, related to the control and the management of gastrointestinal cancers. Mechanistically, curcumin exerts its biological impacts via antioxidant and anti-inflammatory effects through the interaction with various transcription factors and signaling molecules. Moreover, epigenetic modulators such as microRNAs (miRNAs) have been revealed as novel targets of curcumin. Curcumin was discovered to regulate the expression of numerous pathogenic miRNAs in gastric, colorectal, esophageal and liver cancers. The present systematic review was performed to identify miRNAs that are modulated by curcumin in gastrointestinal cancers.

Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

Psychiatric disorders have a major impact on the global burden of disease while therapeutic interventions remain insufficient to adequately treat a large number of patients. Regrettably, the efficacy of several psychopharmacological treatment regimens becomes apparent only after 4-6 weeks, and at this point, a significant number of patients present as non-responsive. As such, many patients go weeks/months without appropriate treatment or symptom management. Adequate biomarkers for treatment success and outcome prediction are thus urgently needed.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using an immunohistochemical analysis of the expression of antigens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET in general is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers), able to identify specific immune system targets, are under investigation in pre-clinical and clinical settings to better highlight all the mechanisms involved in immunotherapy. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Autism spectrum disorder (ASD) pathophysiology is not completely understood; however, altered inflammatory response and glutamate signaling have been reported, leading to the investigation of molecules targeting the immune-glutamatergic system in ASD treatment. Palmitoylethanolamide (PEA) is a naturally occurring saturated N-acylethanolamine that has proven to be effective in controlling inflammation, depression, epilepsy, and pain, possibly through a neuroprotective role against glutamate toxicity. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in ASD. Studies indicate altered serum/brain levels of PEA and other endocannabinoids (ECBs)/acylethanolamines (AEs) in ASD. Altered PEA signaling response to social exposure and altered expression/activity of enzymes responsible for the synthesis and catalysis of ECBs/AEs, as well as downregulation of the peroxisome proliferator activated receptor-α (PPAR-α) and cannabinoid receptor target GPR55 mRNA brain expression, have been reported. Stress and exposure to exogenous cannabinoids may modulate ECBs/AEs levels and expression of candidate genes for neuropsychiatric disorders, with implications for ASD. Limited research suggests that PEA supplementation reduces overall autism severity by improving language and social and nonsocial behaviors. Potential neurobiological underpinnings include modulation of immune response, neuroinflammation, neurotrophy, apoptosis, neurogenesis, neuroplasticity, neurodegeneration, mitochondrial function, and microbiota activity, possibly through peroxisome proliferator-activated receptor-α (PPAR-α) activation.

The immunological findings from autopsies, biopsies, and various studies in COVID-19 patients show that the major cause of morbidity and mortality in COVID-19 is excess immune response resulting in hyper-inflammation. With the objective to review various mechanisms of excess immune response in adult COVID-19 patients, Pubmed was searched for free full articles not related to therapeutics or co-morbid sub-groups, published in English until 27.10.2020, irrespective of type of article, country, or region. Joanna Briggs Institute's design-specific checklists were used to assess the risk of bias. Out of 122 records screened for eligibility, 42 articles were included in the final review. The review found that eventually, most mechanisms result in cytokine excess and up-regulation of Nuclear Factor-κB (NF-κB) signaling as a common pathway of excess immune response. Molecules blocking NF-κB or targeting downstream effectors like Tumour Necrosis Factor α (TNFα) are either undergoing clinical trials or lack specificity and cause unwanted side effects. Neutralization of upstream histamine by histamine-conjugated normal human immunoglobulin has been demonstrated to inhibit the nuclear translocation of NF-κB, thereby preventing the release of pro-inflammatory cytokines Interleukin (IL) 1β, TNF-α, and IL-6 and IL-10 in a safer manner. The authors recommend repositioning it in COVID-19.

Euchromatic histone lysine methyltransferase-2, also known as G9a, is a ubiquitously expressed SET domain-containing histone lysine methyltransferase linked with both facultative and constitutive heterochromatin formation and transcriptional repression. It is an essential developmental gene and reported to play role in embryonic development, establishment of proviral silencing in ES cells, tumor cell growth, metastasis, T-cell immune response, cocaine induced neural plasticity and cognition and adaptive behavior. It is mainly responsible for carrying out mono, di and tri methylation of histone H3K9 in euchromatin. G9a levels are elevated in many cancers and its selective inhibition is known to reduce the cell growth and induce autophagy, apoptosis and senescence. We carried out a thorough search of online literature databases including Pubmed, Scopus, Journal websites, Clinical trials etc to gather the maximum possible information related to the G9a. The main messages from the cited papers are presented in a systematic manner. Chemical structures were drawn by Chemdraw software. In this review, we shed light on current understanding of structure and biological activity of G9a, the molecular events directing its targeting to genomic regions and its post-translational modification. Finally, we discuss the current strategies to target G9a in different cancers and evaluate the available compounds and agents used to inhibit G9a functions. The review provides the present status and future directions of research in targeting G9a and provides the basis to persuade the development of novel strategies to target G9a -related effects in cancer cells.

Thrombopoietin receptor agonist (TPO-RA) treatment increases the thrombosis rate in immune thrombocytopenia (ITP). We hypothesize that TPO-RAs influence platelet function, global and secondary hemostasis and/or fibrinolysis. A systematic review was performed. If possible, data were compared between responders (relevant increase in platelet count), and non-responders. Twelve observational studies with 305 patients were included (responders (127/150 (85%))). There were indications that TPO-RA treatment enhanced platelet function, with respect to platelet-monocyte aggregates, soluble P-selectin, GPVI expression, and adhesion under flow. Studies addressing global and secondary hemostasis and fibrinolysis were scarce. Overall, no changes were found during TPO-RA treatment, apart from an accelerated clot formation and conflicting data on levels of plasminogen activator inhibitor (PAI)-1. The parameters that increased have previously been associated with thrombosis in other patient groups, and might contribute to the increased rate of thrombosis observed in TPO-RA-treated ITP patients.

Bufalin is an anticancer drug extract from traditional Chinese medicine. Several articles about bufalin have been published. However, the literature on bufalin has not yet been systematically studied. This study aimed to identify the study status and knowledge structures of bufalin and to summarize the antitumor mechanism. Data were retrieved and downloaded from the PubMed database. The softwares of BICOMB, gCLUTO, Ucinet 6.0, and NetDraw2.084 were used to analyze these publications. The bufalin related genes were recognized and tagged by ABNER software. Then these BF-related genes were performed by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and protein-protein interaction (PPI) network analysis. A total of 474 papers met the search criteria from 2000 to 2019. By biclustering clustering analysis, the 50 high-frequency main MeSH terms/subheadings were classified into 5 clusters. The clusters of drug therapy and the mechanism of bufalin were hotspot topics. A total of 50 genes were identified as BF-related genes. PPI network analysis showed that inducing apoptosis was the main effect of bufalin, and apoptosis-related gene Caspase 3 was the most reported by people. Bufalin could inhibit the proliferation, invasion, and metastasis of cancer cells through multiple signaling pathways, such as PI3K/AKT, Hedgehog, MAPK/JNK, Wnt/[Formula: see text]-catenin, TGF-[Formula: see text]/Smad, Integrin signaling pathway, and NF-KB signaling pathway via KEGG analysis. Through the quantitative analysis of bufalin literature, we revealed the research status and hot spots in this field and provided some guidance for further research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging virus that is highly pathogenic and has caused the recent worldwide pandemic officially named coronavirus disease (COVID-19). Currently, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Vaccines, such as inactivated vaccines, nucleic acid-based vaccines, and vector vaccines, have already entered clinical trials. In this review, we provide an overview of the experimental and clinical data obtained from recent SARS-CoV-2 vaccines trials, and highlight certain potential safety issues that require consideration when developing vaccines. Furthermore, we summarize several strategies utilized in the development of vaccines against other infectious viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), with the aim of aiding in the design of effective therapeutic approaches against SARS-CoV-2.

Air pollution is a substantial environmental threat to children and acts as acute and chronic disease risk factors alike. Several studies have previously evaluated epigenetic modifications concerning its exposure across various life stages. However, findings on epigenetic modifications as the consequences of air pollution during childhood are rather minimal. This review evaluated highly relevant studies in the field to analyze the existing literature regarding exposure to air pollution, with a focus on epigenetic alterations during childhood and their connections with respiratory health effects. The search was conducted using readily available electronic databases (PubMed and ScienceDirect) to screen for children's studies on epigenetic mechanisms following either pre- or post-natal exposure to air pollutants. Studies relevant enough and matched the predetermined criteria were chosen to be reviewed. Non-English articles and studies that did not report both air monitoring and epigenetic outcomes in the same article were excluded. The review found that epigenetic changes have been linked with exposure to air pollutants during early life with evidence and reports of how they may deregulate the epigenome balance, thus inducing disease progression in the future. Epigenetic studies evolve as a promising new approach in deciphering the underlying impacts of air pollution on deoxyribonucleic acid (DNA) due to links established between some of these epigenetic mechanisms and illnesses.