Interleukin 27 (IL-27) is a cytokine consisting of two subunits, p28 and EBI3, and is a key mediator in regulating the differentiation of TCD4 + cells while playing a crucial role in immune-related disorders. This study aims to elucidate the possible association between IL-27p28 single nucleotide polymorphisms (SNPs), IL-27 serum levels, and the risk of allergic rhinitis (AR).

Blood samples were collected from 130 patients with AR and 130 healthy individuals, and DNA and serum were separated. The relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR was evaluated using the polymerase chain reaction-restriction fragment length polymorphism method. The serum levels of IL-27 in the participants were determined using enzyme-linked immunosorbent assay.

Our results did not show a significant relationship between IL-27p28 SNPs (rs153109 and rs181206) and the risk of AR or serum IL-27 levels. However, our results showed a significant decrease in the serum level of IL-27 in patients with AR (342 ± 299 pg/mL) compared to healthy subjects (455 ± 274 pg/mL) (p = 0.02).

Our results suggest that IL-27p28 SNPs (rs181206 and rs153109) are not associated with susceptibility to AR, but that decreased serum IL-27 levels may be associated with the development of AR.

Many (+)RNA viruses employ translational recoding mechanisms, such as programmed ribosomal readthrough and ribosomal frameshifting, to direct a fraction of translating ribosomes in the infected cell to recode or bypass a stop codon in the zero reading frame and continue translation, thus producing protein isoforms with distinct functions. This creates a means to regulate both the quantity and time of synthesis of canonical and fusion proteins. The viral programmed ribosomal readthrough and ribosomal frameshifting signals are variable, with some being just short RNA sequences encompassing a stop codon, whereas others require elaborate RNA-RNA and RNA-protein interactions. Within virus evolutionary lineages, a given type of recoding signal is not universal, and its presence may be specific to a virus family, species, or even strain. It is possible that the establishment of virus recoding mechanisms and expression patterns occurs after the appearance of extant virus lineages, and these recoding signals might be acquired on multiple occasions during evolution. Recoding signals are the key regulators of gene expression in several clinically important viruses, such as human immunodeficiency viruses 1 and 2, human T-cell lymphotropic retroviruses, and severe acute respiratory syndrome coronavirus 2, as well as in a number of other animal and plant viruses of concern. The knowledge of viral recoding mechanisms is expected to provide new perspectives for the development of antiviral and synthetic biology strategies.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with limited treatment options. Inflammation caused by metabolic disturbances plays a significant role in NAFLD development. Stimulator of interferon gene (STING), a critical regulator of innate immunity, induces the production of interferons and other pro-inflammatory factors by recognizing cytoplasmic DNA to defend against pathogen infection. The STING-mediated signaling pathway appears to play a vital role in hepatic inflammation, metabolic disorders, and even carcinogenesis. Promisingly, pharmacological interventions targeting STING have shown improvements in the pathological state of NAFLD. Macrophages, dendritic cells, natural killer cells, and T cell pathways regulated by STING present potential novel druggable targets for NAFLD treatment. Further research and development in this area may offer new therapeutic options for managing NAFLD effectively.

Nanoparticle (NP) drug delivery systems have been developed recently to resolve the obstacle of drug resistance, contributing to the effective drug delivery to the target organ. A comparative study was carried out herein between doxorubicin (DOX), doxorubicin-loaded titanium NPs, DOX-loaded lactoferrin NPs, DOX-NPs, and PEGylated-doxorubicin (PEG-DOX) on the reno-carcinogenic impact of 3-methylcholanthrene (CA).

In-vivo models were exposed to CA at a dose of 50 mg/kg body weight and left for 3 months till the incidence of chronic kidney disease, followed by one month of treatment with the aforementioned nanomedicines.

CA downregulated DOX resistance biomarkers, including the gene expression of KRAS, FKBP5, P53, and JAK2, and the kidney tumor marker arginase II. In addition, CA increased the levels of the kidney biomarkers creatinine and urea as well as the minerals chloride and magnesium. Decreased gene expression of FKBP5, KRAS, P53, and JAK2 was reversed after the treatment with DOX-loaded titanium NPs, DOX-NPs, DOX-loaded lactoferrin NPs, and PEG-DOX. PEG-DOX abolished the detrimental effects of CA via upregulating the gene expression of the immunophilin protein (FKBP5), the oncogene (KRAS), the tumor suppressor gene (P53), and JAK2, which indicate DOX drug resistance via regulating cell differentiation, division and apoptosis.

PEG-DOX restored renal function and resolved DOX resistance via KRAS, FKBP5, P53, and JAK2 signaling pathways manipulation; consequently, PEG-DOX may provide a useful adjunct treatment for chronic kidney disease.

Sinonasal mucosal melanoma (SNMM) is a rare aggressive malignancy that presents with dismal outcomes and a high metastatic propensity. The prognostic factors as well as therapeutic regimens remain largely unknown due to the rarity of SNMM. This study aimed to assess the characteristics of SNMM patients associated with a better prognosis.

We performed an observational cross-sectional study to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and anti-programmed death-ligand 1 (PD-L1) therapy in 12 SNNM patients who were diagnosed at our institution and treated with anti-PD-L1 from 2011 to 2021.

Of the 12 cases, five (41.7%) displayed brisk TIL activity, while seven (58.3%) had non-brisk TIL activity. The BRAF V600E mutation was not identified in any of the 12 cases by mutational analysis. The expression of PD-L1 was identified in 5 out of 10 SNMM cases (50%). Brisk TILs might be associated with a better prognosis compared with non-brisk TILs (p = 0.036).

Brisk TILs might serve as a potential prognostic factor in SNMM patients. Anti-PD-L1 therapy may be used as a potential therapeutic strategy for treating SNMM.

Hepatic diseases have constituted a significant global problem for over two decades, numerous factors contribute to these diseases, and most eventually result in hepatocellular carcinoma. A particular pivotal factor responsible for hepatic diseases is the abnormal functioning of various metabolic processes. Pyruvate kinase is a crucial regulator of the glycolytic pathway, and overexpression of pyruvate kinase isoform M2 (PKM2) has been observed with various hepatic abnormalities due to genetic malfunctioning and other contributing factors. The present scenario for diagnosing and treating hepatic diseases includes surgery and immunosuppressant therapies. Kinase modulation may also be a potential therapeutic measure for rectifying hepatic diseases, and this can serve as a potential approach. This review summarizes the malfunctions and significance of PKM2 regulation and explores the potential of PKM2 as a target for treating hepatic abnormalities.

Understanding the characteristics of cancer cells is critical for developing enhanced therapies and diagnoses. The super-enhancer notion has been given from the angle of gene regulation in order to properly appreciate the molecular mechanisms behind the identities of distinct cell types. A variety of distinguishing features of super-enhancers have contributed to the findings which link gene regulation and biomolecular condensates. This is typically mediated via liquid-liquid phase separation. Several lines of evidence have pointed to alterations in molecular and biophysical principles in cancer cells, notably those linked to gene regulation and cell signaling. All these findings hint to biomolecular condensate change as a major mechanism by which cancer cells acquire distinct cancer characteristic traits and offer functional innovation for cancer initiation and progression. Liquid-liquid phase separation has recently been used for sorting all the processes taking place in the cell for the formation of biomolecular condensates (membrane-free organelles). Recent studies on biomolecular condensates have found that their production and regulation are associated with cancer. Here, we review the evidence that production and degradation of biomolecular condensates are linked to cancer development and progression. As they are linked to cancers, they can be used in cancer research and to devise new cancer therapies, for example, condensate perturbation.

This study provides a high-level discussion, conclusion, and recommendations on the underutilization of human papilloma virus vaccination (HPVV) in Saskatchewan, Canada, drawing on the findings of individual and group interviews conducted as a part of a qualitative mixed-method study. It is structured in the following way. First, it reiterates key findings from the overall study at the system, provider, and patient levels by locating them in the published literature. Second, it identifies and discusses cross-cutting themes (from the themes identified) at three levels (system, provider, and patient). It then provides a concluding section drawing from our qualitative effort to address the overarching goal of addressing inequitable HPVV uptake by advocating “systems thinking” to enhance overall HPVV uptake. It concludes by providing broad recommendations and implications.

In the etiology of a large number of metabolic disorders, free radicals are involved in the first line, in particular in the physiopathology of cancers. This interventional study aimed to evaluate in vitro the DPPH radical scavenging activity of a hydroalcoholic extract of Cymbopogon citratus (HAECC) and its antiproliferative activity in human osteosarcoma.

The antiproliferative activity of HAECC was assessed in vitro in MG-63 human osteosarcoma cells. Normal rabbit fibroblasts were used to evaluate the biocompatibility of a plant extract. Cell viability was assessed by the 3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test (MTT test). The antiradical activity of HAECC was also evaluated in vitro with the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Moreover, total flavonoid content of HAECC was quantified by the aluminum chloride colorimetric method.

At low concentrations, the HAECC had high antiradical activity (p < 0.001), although it was lower than that of the ascorbic acid standard. HAECC (final concentration of 125 and 250 µg/mL) compared with the vehicle (DMSO 1%) did not affect normal fibroblast viability (p > 0.05) but significantly inhibited the proliferation of MG-63 tumor cells (p < 0.5) inducing a delay in tumor growth without complete suppression. HAECC had more pronounced cytotoxic activity on MG-63 cancer cells (p < 0.05) than on normal cells (p > 0.05). The HAECC had a high total flavonoid content of 4.127333 ± 0.205 mg quercetin equivalent/100 mg extract.

The HAECC contained active antiproliferative compounds with synergistic cytotoxic effects on a cancer cell line.

Endoscopic biopsy and histopathological examination remain one of the critical methods for high-risk subjects (HRS) screening for esophageal squamous cell carcinoma (ESCC) in symptom-free subjects (SFS) of high-incidence areas (HIA) for ESCC. Almost 90% of the symptom-free residents show normal esophageal epithelia in HIA of ESCC. Based on that, overexamination by endoscopy was found in the screening of early ESCC. Furthermore, in large-scale screening on SFS in HIA of ESCC, the application of endoscopy is limited because of the complicated protocol, high cost, and shortage of experienced endoscopists. The authors suggest a two-step screening method. The first step involves a non-invasive serological screening by which to determine the blood level of neoplasm-related molecules which indirectly reflects the esophageal epithelial lesions. Endoscopic and histopathological examinations are involved in the second step. The second step will decrease the screening cost and improve the effectiveness of endoscopic examination for large-scale screening in HIA of ESCC. It is crucial to combine the two steps within a cooperative medical system in rural villages and communities in cities for extensive application.

The gut microbiome has been well-established in its role of regulating the onset of many gastrointestinal disorders. Recent evidence has shown a bidirectional relationship between the intestinal microbiota and the liver. The gut microbiome may affect liver disease progression through its bacterial composition, the metabolism of bile acids, and the translocation of bacterial products. Modulation of dysbiosis may be considered as a potential therapeutic target for liver disease regardless of the underlying cause. Continuing to identify parts of the gut-liver axis that are disordered in different etiologies of liver disease may offer insight into potential interventions to restore homeostasis. Thus, this review will focus on exploring some of the major gut microbiome targeted therapies for liver disease, including probiotics, prebiotics, and fecal microbiota transplantation.

Colorectal cancer (CRC) ranks third in incidence and second in mortality worldwide. In Ecuador, there are 2,481 new CRC cases per year and 2,366 cancer deaths yearly. CRC presents in stages III-IV in more than 50% of patients. The standard treatment for CRC is chemotherapy, with an overall survival (OS) of 29–31 months. The status of biomarkers KRAS, NRAS, BRAF, and MSI provides prognostic and predictive value. This study aimed to determine OS and progression-free survival (PFS) for metastatic CRC based on these molecular markers with a minimum follow-up of one year.

This was an observational longitudinal analytical study at the Hospital de Especialidades Eugenio Espejo (HEEE). We obtained demographic, anatomopathological-molecular, and clinical data from the medical records of patients with metastatic CRC from July 1, 2018 until December 31, 2020.

Data were collected from a total of 177 patients. The median follow-up was 21.6 months. The median PFS was 15 months (11.6–18.3) in those with mutated (MT) markers, 18 months (15.7–20.2) for wild type (WT), and 9 months (4.1–13.8) for not performed markers (NR), with a hazard ratio (HR) for PFS in MT versus WT of 0.76; the 95% confidence interval (CI) (0.4–1.4) with p = 0.4. for OS was 21 months (17.1–24.8) for MT markers, 22 months (17.7–26.2) for WT markers, and 19 months (17.7–20.2) for NR. There were no significant differences in OS for MT vs. WT: HR = 1.38, 95% CI (0.8–2.3) p = 0.6. There was no significant association between OS or PSF and KRAS, NRAS, BRAF, and MSI mutations. KRAS was the most mutated marker, with a frequency of 40.2%.

In the first monocentric study of mutations in metastatic CRC patients from Ecuador, patients with WT molecular markers reached the most prolonged OS and PFS, and KRAS had the highest mutation frequency. However, further studies with larger sample sizes are required to corroborate our findings.

Over the past decade, the approach to gastrointestinal (GI) neuroendocrine tumors (NETs) has increasingly included endoscopic resection (ER) techniques. Underwater endoscopic mucosal resection (UEMR) has been introduced as a potential alternative to conventional mucosectomy. The objective of this systematic review is to investigate the feasibility and outcomes of UEMR in the treatment of GI NETs and to provide a reference for clinical management options.

A systematic search of PubMed, Cochrane Library, and EMBASE was performed to identify guidelines and primary literature published up to 8 August 2023.

Our review did not find any UEMR results for esophageal NETs. For gastric NETs, there is only one case series pilot study with two patients with G1 tumors, that were completely resected without complications. For duodenal NETs eligible for ER, a total of 11 cases are reported, with success in all procedures. For ileum NETs, there is only one report, for an outlier case. Finally, UEMR is best indicated for rectal tumors, where it is an alternative to endoscopic mucosal resection or endoscopic submucosal dissection techniques, as shown in four comparative studies.

UEMR is presented as a good option for selected cases, as it has notable advantages in that it can achieve a complete histological resection at a lower cost, with a short procedure time, and does not require advanced endoscopic skills to ensure good results.

Cancer remains a significant threat to public health globally. Within the Traditional Chinese Medicine (TCM) framework, cancer is perceived not merely as an isolated disease but as a manifestation of a broader imbalance within the human body. Recent advancements in modern medicine have garnered increased attention toward the integrative approach to cancer therapy, combining conventional treatments with TCM practices focusing on achieving a holistic balance. This article aims to delineate the comprehensive perspective of TCM in integrative cancer therapy, emphasizing its foundational principles of personalized treatment grounded in syndrome differentiation and treatment.

In this systematic review, we evaluated the efficacy, mechanisms and safety of three neuromodulation therapies in patients with gastroesophageal reflux disease (GERD), including the effect of neuromodulation therapies on symptoms and key GERD pathophysiologies, lower esophageal sphincter (LES) pressure, esophageal motility, gastric motility, and parasympathetic activity. The first therapy is LES electrical stimulation using an implantable electrical stimulator, the second is transcutaneous electrical acustimulation, and the third is manual acupuncture.

A systematic review of literature according to the PRISMA guidelines was performed. Online databases searched include Medline (Ovid), Embase, and PubMed. Studies were assessed for inclusion and exclusion criteria with Covidence, a systematic review software.

The analysis included thirteen clinical studies. Four papers included were registered under two open-label trials on ClinicalTrials.gov for LES electrical stimulation; Five randomized trials with sham-treated controls were analyzed for transcutaneous electrical acustimulation; Four studies, including three involving standard therapy controls and one involving sham-treated controls were included for manual acupuncture. All evaluated studies demonstrated significant beneficial effects on GERD symptoms, using patient-completed questionnaires, objective 24-h measurement of esophageal pH, and patient-reported use of proton pump inhibitors. In evaluating the effect on key GERD pathophysiologies, electrical stimulation significantly increased LES pressure, and transcutaneous electrical acustimulation significantly improved esophageal motility, gastric motility, and parasympathetic activity. None of the evaluated neuromodulation methods produced severe adverse effects.

Cumulative evidence from the evaluated studies indicates that neuromodulation therapies were effective in treating the GERD symptoms and key underlying GERD pathophysiologies. They are thus valuable options for individualized GERD treatment.

MicroRNAs (miRNAs) are endogenous small noncoding RNAs that regulate gene expression by either degrading or inhibiting the translation of mRNAs and have significant roles in the development of various tumors. A polymorphism (rs2682818) in miR-618 has been confirmed to be correlated with susceptibility to various cancers. Nonetheless, its role has not been investigated in neuroblastoma to date. Therefore, we assessed whether the miR-618 rs2682818 C>A polymorphism was correlated with neuroblastoma risk in the Chinese population.

We performed this case-control study with 402 neuroblastoma patients and 473 cancer-free controls from Jiangsu Province, China. The TaqMan method was used to genotype the miR-618 rs2682818 polymorphism. We evaluated the strength of the correlation between this polymorphism and susceptibility to neuroblastoma based on the odds ratios (ORs) and 95% confidence intervals (CIs), which were calculated by logistic regression models.

Overall, no significant correlation was observed between the rs2682818 C>A polymorphism and the risk of neuroblastoma. Nevertheless, we conducted a further stratification analysis and discovered that, compared to the CC genotype of rs2682818, the subjects with CA/AA genotypes had a lower risk to neuroblastoma developing in the adrenal gland (adjusted OR = 0.57, 95% CI: 0.35–0.91, p = 0.018).

We first discovered that the miR-618 rs2682818 C>A polymorphism had an essential role in significantly decreasing susceptibility to neuroblastoma in the adrenal gland.

Renal function is the basic focus of examination before kidney cancer surgery and determines the choice of surgery procedure. The prediction of renal function after surgery may also affect the surgical method, and it will certainly affect the prognosis of the patient. Herein, we provide a review of the relevant literature on partial nephrectomy (PN) and radical nephrectomy (RN) respectively, discuss methods for estimating kidney function, and compare effects. We found that the most reliable way to predict new baseline glomerular filtration rate (GFR) after PN was the quantitative estimation of the Percent of Preserved Parenchymal Mass (PPPM), while the simplest way to predict new-baseline GFR after RN was derivation from contralateral kidney, with ≥45 mL/min/1.73 m2 considered a good cutoff to evaluate the kidney function and survival outcomes. In addition, based on AI, the imaging-guided analysis would provide a feasible, simple, and reliable prediction model.

Host-specific genetics, such as epigenetic profiles and genetic variants, can contribute to the pathogenesis of infectious diseases. Strong associations have been previously identified in infections by human immunodeficiency virus (HIV), Plasmodium falciparum, norovirus, and influenza A virus. Despite the efforts to characterize the role of host genetics in severe acute respiratory syndrome virus coronavirus 2 (SARS-CoV-2) infection, this comprehension remains incipient. Coronavirus disease 2019 (COVID-19) can evolve with a wide spectrum of manifestations, ranging from asymptomatic and mild cases to severe forms with acute respiratory distress syndrome, multi-organ complications, and even death. Classic clinical risk factors only partially explain this interindividual variability, suggesting that host genetics may contribute to the heterogeneity of courses. Robust evidence has revealed the multiple associations of genes (ABO, PPP1R15A, SLC6A20, IFNAR2, OAS, TYK2, CCR2, CCR5, TLR7, ApoE, TMPRSS2, HLA, ACE2, etc.) with the susceptibility and/or severity of SARS-CoV-2 infection. In addition, the genetics behind the established risk factors have been considered: at least four loci associated with COVID-19 severity (DPP9, FOXP4, SFTPD and MUC5B) have been previously linked to lung fibrosis, interstitial lung disease, lung carcinomas, and/or decreased lung function. In summary, identifying the host-specific genetic factors may improve our knowledge of risk groups for infection and severe outcomes, as well as the biological mechanisms of therapeutic relevance. Therefore, the present literature review aims to understand the genetics underlying the patterns of susceptibility and prognosis of COVID-19.