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Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for the treatment of intestinal inflammation. To improve the bioavailability of ECN-pE in the gastrointestinal tract, chitosan and sodium alginate, effective biofilms, were used to coat ECN-pE via a layer-by-layer electrostatic self-assembly strategy. In a mouse IBD model induced by different chemical drugs, chitosan/sodium alginate coating ECN-pE (ECN-pE(C/A) 2 ) effectively relieved inflammation and repaired epithelial barriers in the colon. Unexpectedly, such engineered EcN-pE(C/A) 2 could also regulate the intestinal microbial communities and improve the abundance of Lachnospiraceae _NK4A136 and Odoribacter in the intestinal flora, which are important microbes to maintain intestinal homeostasis. Thus, this study lays a foundation for the development of living therapeutic proteins using probiotics to treat intestinal-related diseases. Inflammatory bowel disease (IBD) is a complex disease that is associated with multiple genetic and environmental variables. Here the authors develop genetically engineered probiotics with selfproducing functional proteins and biofilm self-coating for safe and efficient IBD treatment in mice.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome (SARS)–like coronavirus (SARS-CoV-2), presents an urgent health crisis. More recently, an increasing number of mutated strains of SARS-CoV-2 have been identified globally. Such mutations, especially those on the spike glycoprotein to render its higher binding affinity to human angiotensin-converting enzyme II (hACE2) receptors, not only resulted in higher transmission of SARS-CoV-2 but also raised serious concerns regarding the efficacies of vaccines against mutated viruses. Since ACE2 is the virus-binding protein on human cells regardless of viral mutations, we design hACE2-containing nanocatchers (NCs) as the competitor with host cells for virus binding to protect cells from SARS-CoV-2 infection. The hACE2-containing NCs, derived fromthe cellular membrane of genetically engineered cells stably expressing hACE2, exhibited excellent neutralization ability against pseudoviruses of both wild-type SARS-CoV-2 and the D614G variant. To prevent SARS-CoV-2 infections in the lung, themost vulnerable organ for COVID-19, we develop an inhalable formulation by mixing hACE2-containing NCs with mucoadhesive excipient hyaluronic acid, the latter of which could significantly prolong the retention of NCs in the lung after inhalation. Excitingly, inhalation of our formulation could lead to potent pseudovirus inhibition ability in hACE2-expressing mouse model, without imposing any appreciable side effects. Importantly, our inhalable hACE2-containing NCs in the lyophilized formulation would allow long-term storage, facilitating their future clinical use. Thus, this work may provide an alternative tactic to inhibit SARS-CoV-2 infections even with different mutations, exhibiting great potential for treatment of the ongoing COVID-19 epidemic.

Oxidative stress, resulting from excessive reactive oxygen species (ROS), plays an important role in the initiation and progression of inflammatory bowel disease (IBD). Therefore, developing novel strategies to target the disease location and treat inflammation is urgently needed. Herein, we designed and developed a novel and effective antioxidant orally-administered nanoplatform based on simulated gastric fluid (SGF)-stabilized titanium carbide MXene nanosheets (Ti C NSs) with excellent biosafety and multiple ROS-scavenging abilities for IBD therapy. This broad-spectrum and efficient ROS scavenging performance was mainly relied on the strong reducibility of Ti-C bound. Intracellular ROS levels confirmed that Ti C NSs could efficiently eliminate excess ROS against oxidative stress-induced cell damage. Following oral administration, negatively-charged Ti C NSs specifically adsorbed onto the positively-charged inflamed colon tissue via electrostatic interaction, leading to efficient therapy of dextran sulfate sodium salt (DSS)-induced colitis. The therapeutic mechanism mainly attributed to decreased ROS levels and pro-inflammatory cytokine secretion, and increased M2-phenotype macrophage infiltration and anti-inflammatory cytokine secretion, efficiently inhibiting inflammation and alleviating colitis symptoms. Due to their excellent ROS-scavenging performance, Ti C -based woundplast also promoted skin wound healing and functional vessel formation. Our study introduces redox-mediated antioxidant MXene nanoplatform as a novel type of orally administered nanoagents for treating IBD and other inflammatory diseases of the digestive tract.

Objective: The geriatric nutritional risk index (GNRI) has found utility as a predictor of outcomes in several malignancies. However, does it predicts outcomes in hepatocellular cancer (HCC) is unclear. In this review, we present high-quality evidence on the prognostic ability of GNRI for HCC. Methods: Two reviewers screened the websites of Embase, PubMed, Web of Science, and Scopus up to 20th June 2024 for relevant articles. We examined overall survival (OS) and progression-free survival (PFS) based on low vs high GNRI in HCC. Results: Total 13 studies were included. Meta-analysis of 11 studies showed that low GNRI was significantly associated with poor OS (HR: 1.83 95% CI: 1.47, 2.29 I2=67%) and PFS (HR: 1.51 95% CI: 1.34, 1.69 I2=27%.) in HCC patients. No publication bias was noted. Most outcomes did not change on subgroup analysis based on country of origin, sample size, Child-Pugh Grade-B %, treatment, cut-off, follow-up, and method of analysis. Results remained significant on sensitivity analysis. Conclusions: The GNRI can predict OS and PFS in HCC patients. Given its availability and ease of calculation, the tool can be incorporated into clinical practice to rapidly predict the prognosis of HCC patients. doi: https://doi.org/10.12669/pjms.41.4.11962 How to cite this: Fang L, Chen Z. Geriatric nutritional risk index as a predictor of prognosis in hepatocellular carcinoma: A systematic review and meta-analysis. Pak J Med Sci. 2025;41(4):1244-1252. doi: https://doi.org/10.12669/pjms.41.4.11962 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Background Heart rate, acidosis, consciousness, oxygenation, and respiratory rate (HACOR) have been used to predict noninvasive ventilation (NIV) failure. However, the HACOR score fails to consider baseline data. Here, we aimed to update the HACOR score to take into account baseline data and test its predictive power for NIV failure primarily after 1–2 h of NIV. Methods A multicenter prospective observational study was performed in 18 hospitals in China and Turkey. Patients who received NIV because of hypoxemic respiratory failure were enrolled. In Chongqing, China, 1451 patients were enrolled in the training cohort. Outside of Chongqing, another 728 patients were enrolled in the external validation cohort. Results Before NIV, the presence of pneumonia, cardiogenic pulmonary edema, pulmonary ARDS, immunosuppression, or septic shock and the SOFA score were strongly associated with NIV failure. These six variables as baseline data were added to the original HACOR score. The AUCs for predicting NIV failure were 0.85 (95% CI 0.84–0.87) and 0.78 (0.75–0.81) tested with the updated HACOR score assessed after 1–2 h of NIV in the training and validation cohorts, respectively. A higher AUC was observed when it was tested with the updated HACOR score compared to the original HACOR score in the training cohort (0.85 vs. 0.80, 0.86 vs. 0.81, and 0.85 vs. 0.82 after 1–2, 12, and 24 h of NIV, respectively; all p values < 0.01). Similar results were found in the validation cohort (0.78 vs. 0.71, 0.79 vs. 0.74, and 0.81 vs. 0.76, respectively; all p values < 0.01). When 7, 10.5, and 14 points of the updated HACOR score were used as cutoff values, the probability of NIV failure was 25%, 50%, and 75%, respectively. Among patients with updated HACOR scores of ≤ 7, 7.5–10.5, 11–14, and > 14 after 1–2 h of NIV, the rate of NIV failure was 12.4%, 38.2%, 67.1%, and 83.7%, respectively. Conclusions The updated HACOR score has high predictive power for NIV failure in patients with hypoxemic respiratory failure. It can be used to help in decision-making when NIV is used.

Glycogen synthase kinase-3β (GSK-3β), a serine/threonine protein kinase, has been reported to show essential roles in molecular pathophysiology of many diseases. Mitochondrion is a dynamic organelle for producing cellular energy and determining cell fates. Stress-induced translocated GSK-3β may interact with mitochondrial proteins, including PI3K-Akt, PGC-1α, HK II, PKCε, components of respiratory chain, and subunits of mPTP. Mitochondrial pool of GSK-3β has been implicated in mediation of mitochondrial functions. GSK-3β exhibits the regulatory effects on mitochondrial biogenesis, mitochondrial bioenergetics, mitochondrial permeability, mitochondrial motility, and mitochondrial apoptosis. The versatile functions of GSK-3β might be associated with its wide range of substrates. Accumulative evidence demonstrates that GSK-3β inactivation may be potentially developed as the promising strategy in management of many diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Intensive efforts have been made for exploring GSK-3β inhibitors. Natural products provide us a great source for screening new lead compounds in inactivation of GSK-3β. The key roles of GSK-3β in mediation of mitochondrial functions are discussed in this review.

Lung adenocarcinoma (LUAD) is one of the most common causes of cancer-related death. The role of pyroptosis in LUAD remains unclear. Our study aimed to identify a prognostic signature of pyroptosis-related genes (PRGs) and explore the connection of PRGs with the tumour microenvironment in LUAD. Gene expression and clinical information were obtained from The Cancer Genome Atlas database. Consensus clustering was applied to classify LUAD patients. The least absolute shrinkage and selection operator Cox and multivariate Cox regression models were used to generate a PRG-related prognostic signature. The correlations between PRGs and tumour-infiltrating immune cells or the tumour mutational burden were analysed by Spearman’s correlation analysis. In this study, 44 PRGs significantly differed in expression between LUAD and normal tissues. Based on these genes, patients were clustered into three clusters with significantly different distributions of tumour-infiltrating immune cells and immune checkpoint regulators. A total of four PRGs ( NLRP1 , HMGB1 , CYCS , and BAK1 ) were used to construct a prognostic model. Significant correlations were observed between these prognostic PRGs and immune cell infiltration or the tumour mutational burden. Predictive nomogram results showed that BAK1 could be an independent prognostic biomarker in LUAD. Additionally, the expression level of BAK1 was validated in two independent Gene Expression Omnibus cohorts. Our identified prognostic PRG signature may provide insight for future studies targeting pyroptosis and the tumour microenvironment in LUAD. Future studies are needed to verify our current findings.

Chronic obstructive pulmonary disease (COPD), characterized by persistent and not fully reversible airflow restrictions, is currently one of the most widespread chronic lung diseases in the world. The most common symptoms of COPD are cough, expectoration, and exertional dyspnea. Although various strategies have been developed during the last few decades, current medical treatment for COPD only focuses on the relief of symptoms, and the reversal of lung function deterioration and improvement in patient's quality of life are very limited. Consequently, development of novel effective therapeutic strategies for COPD is urgently needed. Stem cells were known to differentiate into a variety of cell types and used to regenerate lung parenchyma and airway structures. Stem cell therapy is a promising therapeutic strategy that has the potential to restore the lung function and improve the quality of life in patients with COPD. This review summarizes the current state of knowledge regarding the clinical research on the treatment of COPD with mesenchymal stem cells (MSCs) and aims to update the understanding of the role of MSCs in COPD treatment, which may be helpful for developing effective therapeutic strategies in clinical settings.

Objective: This study aims to investigate the clinical pathological features of colorectal lateral spreading tumors (LSTs) with skirt features and the associated carcinogenic risk factors. Methods: A total of 390 cases of colorectal LSTs, treated via endoscopy at the Digestive Endoscopy Center of the 900th Hospital of the People’s Liberation Army Joint Logistics Support Force between January 2021 and August 2023, were included. The cases were categorized into a skirt group (30 cases) and a group without a skirt (360 cases) based on the presence of skirt features. The clinical pathological characteristics, including age, gender, endoscopic features (lesion diameter, location, morphology), and histological types, were compared between the two groups. Additionally, the risk factors for carcinogenesis in LSTs with a skirt were analyzed. Results: Among the 390 LSTs cases, 30 (7.69%) exhibited skirt features, with 23 lesions located in the rectum (76.67%) and 26 lesions having a diameter of ≥ 20 mm (86.67%). Histological classification revealed 10 cases (33.33%) of adenomas with low‐grade intraepithelial neoplasia (LGIN), 9 cases (30.00%) of adenomas with high‐GIN (HGIN), and 11 cases (36.67%) of carcinoma. The proportions of female patients, rectal lesions, lesions with a diameter of ≥ 20 mm, mixed nodular lesions, and those classified as carcinoma were significantly higher in LSTs with a skirt group compared to LSTs without a skirt group. Rectal lesions ( p = 0.001, OR = 8.588, 95% CI: 2.428–30.379) and lesion diameters ≥ 20 mm ( p = 0.008, OR = 4.538, 95% CI: 1.477–13.940) were identified as independent predictors of skirt presence in colorectal LSTs. Age ≥ 60 years ( p = 0.002, OR = 22.667, 95% CI: 3.140–163.629) was found to be an independent risk factor for carcinogenesis in LSTs with a skirt. Conclusion: Compared with LSTs without a skirt, the results indicated that LSTs with a skirt are more commonly found in female patients, predominantly has a diameter of ≥ 20 mm, typically presents as a mixed nodular type, is frequently located in the rectum, and is often classified as carcinoma. The presence of rectal lesions and lesion diameter ≥ 20 mm increases the likelihood of skirt features in LSTs. Furthermore, advanced age (≥ 60 years) may elevate the risk of carcinogenesis in LSTs with a skirt, necessitating thorough preoperative assessments and complete resection during endoscopic removal of such lesions.

Subgroup analyses based on country, sex, age, body mass index (BMI), and percent of forced expiratory volume in one second (FEV1%) predicted were performed to explore the source of heterogeneity. Sputum HMGB1 levels were significantly higher in patients with severe asthma than in those with mild-to-moderate asthma, and HMGB1 levels increased with the degree of airflow limitation. [...]HMGB1 could be an independent risk factor affecting the predicted value of FEV1%. Additionally, HMGB1 overexpression was more pronounced in patients with moderate-to-severe and severe asthma than in healthy subjects, suggesting that high HMGB1 levels correlated positively with disease severity. [...]elevated HMGB1 levels may be a potential biomarker of asthma severity. [...]our results suggest that HMGB1 could be a potential biomarker of asthma severity. Funding This work was supported by grants from the National Key Research and Development Program of China (Nos. 2022YFF0710800 and 2018YFC1313600), Major International (Regional) Joint Research Project of China (No. 81820108001), National Natural Science Foundation of China (Nos. 81670029 and 82000038), Jiangsu Key Principal Investigator of Medicine (No.