The International System (TIS) for reporting serous fluid cytopathology was published in December 2020 as a joint project by the International Academy of Cytology and the American Society of Cytopathology. The purpose was to standardize the diagnostic criteria and nomenclature used in reporting serous fluid samples, thereby improving the reproducibility of reports and improving communication between pathologists and clinicians. TIS defines a five-tier system consisting of nondiagnostic, negative for malignancy, atypia of uncertain significance, suspicious for malignancy and malignant categories. This review provides an updated summary of the reporting system, risk of malignancy, potential diagnostic pitfalls, and a practical diagnostic approach to serous fluid specimens.

Helicobacter pylori (H. pylori) is an exceptionally common human pathogen infecting a large proportion of the world’s population. It is known to cause gastritis, peptic ulcer disease, non- cardiac gastric adenocarcinoma, and gastric mucosa-assisted lymphoid tissue lymphoma. Test and treat is a widely practiced strategy for H. pylori infection worldwide. While there are clear benefits of treating H. pylori infection, long-term adverse consequences of widespread eradication of this commonly identified pathogen remain an area of much debate. H. pylori infection affects gastric acid secretion and the relationships of the infection with gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC) have been studied but remain controversial topics. Review of the most up-to-date evidence from studies performed in the last 20 years suggests a possible inverse relationship between the prevalence of H. pylori infection and GERD. A meta-analysis of a randomized controlled trial showed that eradication of the infection was more likely to cause increased incidence of GERD. Additionally, other studies have noted a significant protective effect of H. pylori infection, notably Cag A+ strains, against the development of BE and EAC. In this review article, we will discuss the impact of H. pylori infection status on GERD, BE, and esophageal cancer.

Tumors interact with various populations of nonmalignant cells, such as endothelial, stromal, and immune cells, to create a favorable tumor microenvironment (TME) for invasion and metastasis of cancer cells. A key mechanism for maintaining the pro-oncogenic properties of the TME is the formation of an immunosuppressive environment that allows the tumor to avoid an immune response. A strictly immunosuppressive environment is supported mainly by the activity of engaged immune cells that secrete inflammatory cytokines and factors that inhibit the function of cytotoxic T lymphocytes. On the other hand, the activity of tumor-associated immune cells depends not only on cancer-cell signals but also on microbial metabolites derived from the gut microbiota. The gut microbiota consists of bacteria, viruses, protozoans, archaea, and fungi that influence the host immune response, DNA damage, and chronic inflammation in gastrointestinal and other cancers, such as breast cancer. In particular, intestinal dysbiosis can lead to restructuring of the TME and the promotion of tumor growth. Recently, a wide spectrum of bacterial metabolites, such as short-chain fatty acids, tryptophan catabolites, secondary bile acids, etc., have been shown to have a signaling function that affects not only the formation of the TME but also the response of cancer cells to therapeutic agents, including immunotherapy. Therefore, studying the effects of microbiota metabolites in relation to cancer development and cancer therapy effectiveness is strictly necessary. In this review, we briefly describe key microbiota factors that influence the formation of immunosuppressive TMEs.

Although many patients with hepatocellular carcinoma (HCC) achieved significant prognostic improvement through surgical treatment, rapid and aggressive intrahepatic dissemination within months after radical resection was occasionally encountered. To date, there has been no dedicated literature addressing this phenomenon.

In this case-control study, we proposed the concept of early explosive recurrence (EER), which was defined as simultaneous development of no less than three recurrent lesions involving at least three different Couinaud’s segments within 6 months following radical resection. A total of 325 patients (17 EER patients and 308 controls) were retrospectively reviewed.

The incidence of EER of early HCC patients was 5.2%. EER was manifested as either multiple nodular (n = 11) or diffusely infiltrative type (n = 6). EER patients had significantly worse survival (hazards ratio, 48.7; 95% confidence interval: 19.9, 119.0). At multivariate analysis, increased tumor number, enlarged tumor size, positive microvascular invasion (MVI) and Glypican-3 (GPC3) were significant risk factors for EER. Tumor immune microenvironment (TIME) gene expression profile analysis showed that patients with EER presented higher transcriptional levels of CCL20, NT5E, and TDO2 as well as a lower transcriptional level of HLA-DQ1. Gene set enrichment analysis revealed that gene sets involving Th1 and Th2 differentiation (p = 0.016) and Th17 cell differentiation (p = 0.049) were enriched in control group.

Some surgically treated HCC patients developed EER with poor prognosis. The clinicopathological risk factors of EER included tumor number, tumor size MVI, and GPC3. Specific TIME profiles facilitate intrahepatic metastasis and progression of HCC.

Colorectal cancer is one of the most significant and deadliest malignant tumors among various types of cancers. Due to its generally low overall survival rate, the development of new treatment strategies for early detection and diagnosis, as well as the identification of prognostic markers, has become exceedingly crucial. The molecular mechanism of colorectal cancer remains uncertain and to address this, the aim is to identify key genes, determine in which pathways these genes are involved, explore their interactions with regulatory molecules, and investigate their overall relationship with survival and immune cell infiltration.

After selecting the databases related to colorectal cancer from the Gene Expression Omnibus database, differentially expressed genes were identified. Gene ontology and pathway analyses were then conducted for these genes, and interaction networks with proteins were constructed. Core genes were identified, and their relationship with regulatory molecules such as miRNAs and transcription factors was examined. Additionally, immune cell infiltration and survival analyses were performed.

As a result of the bioinformatic analyses, 71 differentially expressed genes were identified, which were found to overlap in four distinct microarray datasets. Among these differentially expressed genes, Krüppel-like factor 4 (KLF4), CLCA4, GUCA2B, GUCA2A, LGR5, SLC4A4, ZG16, CA7, CA2, and GCG were determined as hub genes. Among the hub genes, CA2, CLCA4, SLC4A4, and KLF4 genes showed a positive correlation with immune cells in immune cell infiltration analyses. The expression levels of these four genes were also confirmed using data from the Human Protein Atlas database. Additionally, only the KLF4 gene was associated with poor prognosis in overall survival analyses.

The obtained results suggest that the KLF4 gene may serve as a potential therapeutic agent.

The cyclic adenosine monophosphate Receptor Protein of Mycobacterium tuberculosis (CRPMt) (Rv3676), is a global transcriptional regulator and plays a pivotal role in the survival and infection of Mycobacterium. This signaling protein (CRPMt) shares several common structural and functional features with the CRP from Escherichia coli. Structurally, CRPMt is a homodimer that undergoes allosteric changes upon cyclic AMP binding. This binding also triggers the activation of several genes responsible for various physiological processes in this bacterium. Despite the importance of CRP for mycobacterial survival, limited information is available regarding the stability and unfolding properties of the protein. The main objective of this study is to study stability, unfolding and dynamics of CRPMT in terms of its structure.

In this study, we monitored the stability and unfolding of CRPMt using various biophysical and computational techniques.

We experimentally studied protein unfolding in the presence of chemical denaturants [urea and guanidine hydrochloride (GdnHCl)]. The results from these chemical-induced unfolding studies suggest that CRPMt follows a two-state transition and that chemical-induced protein denaturation is reversible. According to circular dichroism and activity data, CRPMt structure and function were restored upon refolding. We also studied the stability and unfolding of the CRPMt protein against temperature variations and protease action (trypsin). Limited proteolysis experiments provide insights into the minimum domain structure requirement for CRPMt activity. Interestingly, temperature-induced CRPMt unfolding was completely different compared to chemical-induced unfolding. The thermal unfolding of CRPMt was found to be irreversible, leading to the formation of insoluble aggregates at elevated temperatures. To understand why the thermal unfolding of the protein differed from chemically induced unfolding, we carried out a detailed molecular dynamics simulation analysis of the protein at three different temperatures. The results from these molecular dynamics simulations mechanistically validate the significant differences between chemical and temperature-induced CRPMt unfolding.

Our study provides detailed insights into the stability and folding/unfolding properties of CRPMt, which could be useful in developing new anti-mycobacterial medicines.

Cytokine storm (CS) is an acute systemic inflammatory response with limited effective interventions up to now. The treatment experience of the COVID-19 pandemic suggests great potential in the intervention of CS by herbal medicine. This study aimed to investigate whether Schisanhenol (SSH), an active component of the Chinese herbal medicine Schisandra chinensis, has the potential to inhibit CS.

The effect of SSH on nuclear factor-kappa B (NF-κB) signaling pathway activity was observed with human myeloid leukemia mononuclear Lucia (THP-1)/NF-κB cells. THP-1 and abdominal macrophages were used as cell models to observe the effect of SSH on inflammatory responses. The lipopolysaccharide-induced acute inflammatory response in mice was used to observe the effect of SSH on systemic inflammatory response and induced acute lung injury. The potential biological mechanism of SSH against inflammatory storm was explored by network pharmacology and molecular docking methods.

SSH significantly inhibited NF-κB pathway activity and suppressed macrophages and systemic inflammatory responses in mice. SSH also effectively alleviated lipopolysaccharide-induced acute lung injury. The network pharmacology results showed that estimated glomerular filtration rate, matrix metalloproteinase 9, proto-oncogene tyrosine-protein kinase Src, and mammalian target of rapamycin were potential key target proteins of SSH.

SSH has promise as a potential small molecule of Chinese medicine for clinical treatment and drug development in the inhibition of CS.

Histiocytic disorders are rare in childhood and often present with a wide spectrum of histological and clinical symptoms, making their diagnosis challenging. The pathological classification of histiocytic disorders has been evolving during the last few decades, and new diagnostic criteria and classifications have been recently updated. Herein, we review pediatric histiocytic disorders, focusing on the pathological features of morphology, immunophenotype, and newly discovered molecular data. These insights shed light on the pathogenesis of these disorders and may become therapeutic biomarkers.

Nowadays, Ephedra species have been marked as encouraging natural material for research in the field of pharmacology. This work provides an overview of the botanical, traditional uses, phytochemistry, pharmacological properties, molecular mechanisms, and toxicity of Ephedra alata. The following databases were utilized to search for primary literature references: PubMed, Web of Science, Scopus, Scientific Information Database, Science Direct, Google, and Google Scholar. The present review demonstrates that various compounds have been extracted from E. alata, such as fatty acids, sphingolipids, volatile compounds, reducing sugars, flavonoids, phenolic compounds, and alkaloids. These natural compounds show valuable biological activities, such as antioxidant, antimicrobial, anti-inflammatory, anticancer, antidiabetic, antihypertensive, anti-obesity, nephroprotective, hepatoprotective, antipyretic, analgesic, anti-acetylcholinesterase, antityrosinase, and anti-urease activities. Several mechanisms are proposed to understand the biological effects of E. alata. In summary, E. alata constitutes good natural material for utilization in food and medicine applications.

Mitochondria are the main cell organelles responsible for adenosine triphosphate production through cellular respiration. They also have roles in regulating other cellular processes, including reactive oxygen species, apoptosis, and others. The function and number of mitochondria are important for the maintenance of bone homeostasis. In recent years, the regulation of bone homeostasis by mitochondria has attracted particular interest. In addition, some natural compounds have been demonstrated to modulate mitochondria functions, such as resveratrol, quercetin, and curcumin, etc. Here, we review the recent discoveries concerning mitochondrial oxidative phosphorylation and bone formation, as well as the effects of some natural compounds (resveratrol, quercetin, and curcumin) on oxidative phosphorylation, and discuss their therapeutic implications in treating bone disorders.

Cytokine storm is a severe immune response that is characterized by the release of large amounts of inflammatory mediators (e.g., cytokines). 2′,5′-Dihydroxyacetophenone (DHAP) is a small molecule with a variety of biological activities involving antioxidant, anti-inflammation and antitumor. The primary objective of the current investigation is to elucidate the underlying mechanism of DHAP in cytokine storm and perform a preliminary analysis of its potential applications.

The roles of DHAP in cytokine storm were investigated in vitro and in vivo. The molecular basis of DHAP was also studied by network pharmacological analysis and molecular docking.

DHAP inhibited the production of inflammatory factors such as interleukin-1β, interleukin-6, and nitric oxide, alleviated the symptoms of the inflammatory response, and prolonged the survival of cytokine storm animal models. In vitro experiments showed that DHAP inhibited the proliferation of RAW264.7 cells in an inflammatory environment and suppressed the secretion of pro-inflammatory factors in RAW264.7 cells. Western blot results showed that DHAP increased the protein stability of Hdac1, decreased the acetylation level of P65, and inhibited the activation of the nuclear factor-kappa B signaling pathway.

DHAP protected against cytokine storm by repressing the excessive production of pro-inflammatory factors and attenuating immune responses. DHAP efficiently inactivated the nuclear factor-kappa B signaling pathway. Hdac1 may act as the potential target of DHAP to inhibit cytokine storm. DHAP is a potential treatment of cytokine storm and deserves further study.

Previous studies showed that tumors are associated with the increased inflammatory burden and neutrophil-to-lymphocyte ratio (NLR) is also associated with inflammatory conditions. However, there is no review on the role of NLR in meningioma. The goal of this study was to see if NLR has any prognostic and diagnostic value in meningioma.

The search was conducted on PubMed, Scopus, and Web of Science up to 3 August 2023. A total of 23 studies were included in the systematic review, of which 13 were included in the meta-analysis.

It was found that patients with high-grade meningioma had higher levels of NLR compared to those with low-grade meningioma (standardized mean difference [SMD] = 0.72, 95% confidence interval [CI]: 0.21–1.23, p = 0.006)]. In addition, we found that there was no difference between NLR levels of patients with meningioma and those with gliomas (SMD, −0.19, 95% CI: −0.47–0.10, p = 0.20). Also, higher levels of NLR were found in patients with meningioma compared with healthy controls (SMD = 0.56, 95% CI: 0.24–0.88, p = 0.01). Studies showed that an NLR > 2.4 differentiated high-grade and low-grade meningioma, an NLR > 2.74 differentiated high and low progression-free survival groups, and an NLR > 2.59 was associated with recurrence, with high sensitivity and specificity. However, the NLR did not predict postoperative pneumonia following meningioma resection. Because of the contradiction, our study did not clearly demonstrate the difference in NLR levels in meningioma and other pathologies, so more studies are needed on this subject.

NLR had significant diagnostic and prognostic value in meningioma. In general, we inferred a strong link between systemic inflammation assessed by NLR and meningioma, based on elevated levels of NLR in patients with meningioma compared to healthy controls. In addition, NLR had significant predictive potential for the progression and recurrence of meningioma. The predictive potential increased when combined with other diagnostic tools such as fibrinogen level. NLR may guide clinical decision making as an inflammatory marker and its relationship to therapeutic efficacy.

Our capacity to recognize and manage allosensitized transplant recipients and optimize organ allocation has been greatly improved by the development of single-antigen bead tests for detecting human leukocyte antigen antibodies. The main drawbacks of this technology have been thoroughly discussed in the literature, covering problems like artifacts that result in nonspecific background, variability, lack of uniformity, and difficulties in data interpretation. Consequently, it is not always easy to understand single-antigen bead data. This review will discuss the interpretation of donor-specific antibody data while considering the associated technical limitations. To ensure the correct clinical application of this test and to enhance the quality of antibody data used to support published clinical research in the era of epitope-based computational matching algorithms, a detailed understanding of the single-antigen bead assay is necessary.

Tuberculosis remains a global health concern, and its treatment usually involves potent first-line antitubercular drugs which are tempered by the risk of associated hepatotoxicity leading to noncompliance and drug resistance. In this review, medicinal plants with the potential of protection against antitubercular drug-induced hepatotoxicity in animal models were explored from scientific literatures.

From literature published between 1999 and 2022, this review systematically extracted 68 studies that reported on medicinal plants with protection against antitubercular drug-induced liver toxicity in animal models.

Isoniazid, pyrazinamide, rifampicin, and etambutol were the first-line drugs reported in the reviewed studies. The liver enzymes, antioxidant status, inflammatory markers, and improvement in the liver architecture were the criteria most frequently used by the reported studies to access hepatoprotection. These plants are rich in bioactive phytochemicals which exhibit their hepatoprotective properties via mechanisms such as antioxidant activity, anti-inflammatory effects, and detoxification enhancement.

This review provides the hepatoprotective properties and mode of action of medicinal plants and encourages future perspectives marked by rigorous scientific research, clinical trials, and integrative medicine approaches. Albeit the challenges of standardization of herbal formulation, safety concerns and hurdles of the regulatory framework must be addressed as traditional medicinal plants offer a promise to mitigate antitubercular drug hepatotoxicity.

The insulin/insulin-like growth factor (IGF) system has many receptors, signaling pathways, and ligands, making it highly complex. IGF1 increases the function of germ cells by increasing the synthesis of spermatogonia DNA and slowing down apoptotic cells. One of the most important objectives of this study was to investigate the function of fennel on the expression of the IGF1 gene in Kermani sheep testes.

The study involvedthree levels of fennel in the diets (20, 10, and zero g/kg dry matter), and tissue sampling was performed using testis tissue. Samples were rapidly placed in liquid nitrogen before being stored at -80°C. Then, total RNA was extracted and for the IGF1 gene (target) and GAPDH gene (reference), the real-time polymerase chain reaction was applied.

The outcomes displayed that increasing levels of fennel in the ration significantly (p < 0.05) increases the weight of the testis (0.35 kg and 0.36 kg at the levels of 1% and 2% fennel, respectively) compared to rations without fennel (0.29 kg at the levels of 0%). Association between testosterone and fennel feeding in studied lambs showed that adding fennel to the diet significantly (p < 0.05) increasesthe concentration of blood testosterone (3.5 ng/dL and 4.4 ng/dL at the levels of 1% and 2% fennel, respectively) compared with rations without fennel (1.7 ng/dL). The results showed that adding fennel to the diet significantly (p < 0.05) increases the amount of IGF1 gene expression in the testis (2.5 and 2.7 at the levels of 1% and 2% fennel, respectively) compared with rations without fennel (1 at the levels of 0% fennel).

Fennel has an affirmative effect on gene expression in the testis and can be added to sheep food rations to progress reproductive functions (by stimulating Leydig cell steroidogenesis, producing more sperm and testosterone, and growing and developing the testis).

Patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations benefit from targeted therapy with tyrosine kinase inhibitors (TKIs). Nevertheless, 50–70% of patients will experience progressive disease during TKI therapy, and nearly half will develop resistance mutations such as T790M, for which a third-generation TKI has been developed and proven to be highly effective. One of the most common sites of metastasis in patients with NSCLC is the central nervous system, significantly impacting their and their relatives’ quality of life as well as the management of the disease. A patient diagnosed with stage IV lung adenocarcinoma showed progression after 21 months of first-line anti-EGFR therapy and showed clear signs of neurological impairment. The interpretation of cerebral involvement was dubious and difficult: while cerebral spinal fluid cytology seemed to confirm leptomeningeal carcinomatosis, no meningeal nodules or abnormal enhancement was detected on magnetic resonance imaging. Liquid biopsy detected the resistance mutation T790M; hence, therapy was switched to the third-generation TKI osimertinib. The first instrumental re-evaluation revealed a partial response, with a reduction in both lung lesion dimensions and brain alterations. This case shows the effectiveness of osimertinib in treating patients with stage IV NSCLC with central nervous system and bone involvement.