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Abstract Metabolic reprogramming, a hallmark of tumorigenesis, involves alterations in glucose and fatty acid metabolism. Here, we investigate the role of Carnitine palmitoyl transferase 1a (Cpt1a), a key enzyme in long-chain fatty acid (LCFA) oxidation, in ErbB2-driven breast cancers. In ErbB2+ breast cancer models, ablation of Cpt1a delays tumor onset, growth, and metastasis. However, Cpt1a-deficient cells exhibit increased glucose dependency that enables survival and eventual tumor progression. Consequently, these cells exhibit heightened oxidative stress and upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) activity. Inhibiting Nrf2 or silencing its expression reduces proliferation and glucose consumption in Cpt1a-deficient cells. Combining the ketogenic diet, composed of LCFAs, or an anti-ErbB2 monoclonal antibody (mAb) with Cpt1a deficiency significantly perturbs tumor growth, enhances apoptosis, and reduces lung metastasis. Using an immunocompetent model, we show that Cpt1a inhibition promotes an antitumor immune microenvironment, thereby enhancing the efficacy of anti-ErbB2 mAbs. Our findings underscore the importance of targeting fatty acid oxidation alongside HER2-targeted therapies to combat resistance in HER2+ breast cancer patients.

Abstract Therapeutics that interfere with the damage/pathogen-associated molecular patterns (DAMPs/PAMPs) have evolved as promising candidates for hepatic inflammation like that occurring in non-alcoholic fatty liver disease (NAFLD). In the current study, we examined the therapeutic impact of the phosphodiesterase-1 inhibitor vinpocetine (Vinpo), alone or when combined with Lactobacillus, on hepatic abnormalities caused by a 13-week high-fat diet (HFD) and diabetes in rats. The results show that Vinpo (10 and 20 mg/kg/day) dose-dependently curbed HFD-induced elevation of liver injury parameters in serum (ALT, AST) and tissue histopathology. These effects were concordant with Vinpo’s potential to ameliorate HFD-induced fibrosis (Histological fibrosis score, hydroxyproline, TGF-β1) and oxidative stress (MDA, NOx) alongside restoring the antioxidant-related parameters (GSH, SOD, Nrf-2, HO-1) in the liver. Mechanistically, Vinpo attenuated the hepatocellular release of DAMPs like high mobility group box (HMGB)1 alongside lowering the overactivation of the pattern recognition receptors including, toll-like receptor (TLR)4 and receptor for advanced glycation end-products (RAGE). Consequently, there was less activation of the transcription factor nuclear factor-kappa B that lowered production of the proinflammatory cytokines TNF-α and IL-6 in Vinpo-treated HFD/diabetes rats. Compared to Vinpo treatment alone, Lactobacillus probiotics as adjunctive therapy with Vinpo significantly improved the disease-associated inflammation and oxidative stress injury, as well as the insulin resistance and lipid profile abnormalities via enhancing the restoration of the symbiotic microbiota. In conclusion, combining Vinpo and Lactobacillus probiotics may be a successful approach for limiting NAFLD in humans.

Technology-enhanced assessment (TEA) means all types of assessments that use technological aid either online or offline, either during or after learning with the objective of improving or assessing the process of learning. Aims: This study assessed the effectiveness and influence of TEA on the academic performance of medical students in a Malaysian private university. A cross-sectional study was conducted and convenience sampling was applied to recruit participants. A validated online questionnaire was used and the participants were required to report their demographic characteristics, academic performance before and after using TEA, and their attitudes towards the TEA. Paired-t-test was performed to assess the difference in medical students’ mean CGPA before and after using TEA. Study findings showed that medical students have positive attitudes towards TEA and believe that TEA offers value to their learning. TEA was found to have a positive impact on the academic performance by which there is a significance difference in medical students’ mean CGPA before and after using TEA (p0.05). TEA is an effective tool that can enhance the learning process among medical students. Nevertheless, the sample studied need to be more diverse to be able to generalize the results for all medical students along different universities and countries.

Article accepted. The article will be published here soon. Pending final quality checks.

The current investigation aims to study the bio route preparation of chitosan capped-silver nanoparticles using aqueous flower extract of the Achillea ptarmica plant. The biosynthesized silver nanoparticles/chitosan (Ag NPs@CHI) were characterized by various spectroscopic techniques. The creation of Ag nanoparticles over the chitosan was initially determined by the presence of a single broad peak at 545 nm that was recorded by the UV–Vis spectrum. The presence of poly-dispersity, spherical shape and nanosizes in the Ag NPs@CHI were verified by the TEM and SEM pictures. The purity and crystalline nature of the prepared Ag NPs@CHI were confirmed by XRD analysis. In vivo, Ag NPs@CHI decreased the inflammatory cells presence in the colon and ileum, lowered the levels of IL-17A, IL-1β, IL-6, and TNF-α, raised the levels of IL-10 and IL-4 in colon tissues, enhanced acetate and propionate production. The findings revealed that Ag NPs@CHI have the potential to boost intestinal structure restoration, decrease levels of inflammatory cytokines and enhance short-chain fatty acid (SCFA) levels. Our research demonstrated that Ag NPs@CHI can safeguard the intestinal barrier by upregulating the expression of Claudin-1 and Occludin. Furthermore, silver nanoparticles suppressed the MAPK signaling pathway to ameliorate the inflammatory condition. Following the completion of clinical trials, these novel nanoparticles could serve as a promising new treatment for diarrhea in humans.

PIPAC is a new surgical procedure and a viable treatment option for PSM patients, due to promising therapeutic outcomes, minimal invasiveness, limited surgical morbidity, and systemic toxicity side effects. However, its implementation throughout hospitals is hard to obtain due to its fragile economical sustainability. A retrospective health economic analysis was conducted in order to evaluate the cost of hospitalization for patients undergoing PIPAC treatment at Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, in Rome. The average cost of a PIPAC procedure was defined based on the cost of surgery (cost of surgical material, operating room, intraperitoneal chemotherapy), hospital stay, diagnostic examinations, and drugs used during the stay. A total of 493 PIPAC procedures were performed on 222 patients with peritoneal metastases or primary peritoneal cancer from 2017 to 2023. Since the mean remuneration for each PIPAC hospitalization is €5916 and the mean expenditure per hospitalization is €6538, this results in an operating profit per PIPAC hospitalization of −€622. The reimbursement of PIPAC treatment by the Italian National Health System currently only partially covers the hospital’s costs. Development of specific codes and adequate reimbursement for PIPAC by recognizing this procedure as a proper treatment for peritoneal carcinomatosis is essential.