MiR-9-1 Suppresses Cell Proliferation and Promotes Apoptosis by Targeting UHRF1 in Lung Cancer

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 to 1. The inhibition of UHRF1 by miR-9 to 1 causes G1 arrest and p15, p16, and p21 were re-expressed in miR-9 to 1 group in mRNA level and protein level. Silence of UHRF1 expression in A549 cells resulted in the similar re-expression of p15, p16, p21 which is similar with miR-9 to 1 infection. Therefore, we concluded that UHRF1 is a new target for miR-9 to 1 to suppress cell proliferation by re-expression of tumor suppressors p15, p16, and p21 mediated by UHRF1

Mechanism and intervention of murine transfusion-related acute lung injury caused by anti-CD36 antibodies

Anti-CD36 Abs have been suggested to induce transfusion-related acute lung injury (TRALI) upon blood transfusion, particularly in Asian populations. However, little is known about the pathological mechanism of anti-CD36 Ab–mediated TRALI, and potential therapies have not yet been identified. Here, we developed a murine model of anti-CD36 Ab–mediated TRALI to address these questions. Administration of mouse mAb against CD36 (mAb GZ1) or human anti-CD36 IgG, but not GZ1 F(ab′)2 fragments, induced severe TRALI in Cd36+/+ male mice. Predepletion of recipient monocytes or complement, but not neutrophils or platelets, prevented the development of murine TRALI. Moreover, plasma C5a levels after TRALI induction by anti-CD36 Abs increased more than 3-fold, implying a critical role of complement C5 activation in the mechanism of Fc-dependent anti-CD36–mediated TRALI. Administration of GZ1 F(ab′)2, antioxidant (N-acetyl cysteine, NAC), or C5 blocker (mAb BB5.1) before TRALI induction completely protected mice from anti-CD36–mediated TRALI. Although no significant amelioration in TRALI was observed when mice were injected with GZ1 F(ab′)2 after TRALI induction, significant improvement was achieved when mice were treated postinduction with NAC or anti-C5. Importantly, anti-C5 treatment completely rescued mice from TRALI, suggesting the potential role of existing anti-C5 drugs in the treatment of patients with TRALI caused by anti-CD36

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large-Vessel Occlusion Stroke

Importance It is uncertain whether intravenous methylprednisolone improves outcomes for patients with acute ischemic stroke due to large-vessel occlusion (LVO) undergoing endovascular thrombectomy. Objective To assess the efficacy and adverse events of adjunctive intravenous low-dose methylprednisolone to endovascular thrombectomy for acute ischemic stroke secondary to LVO. Design, Setting, and Participants This investigator-initiated, randomized, double-blind, placebo-controlled trial was implemented at 82 hospitals in China, enrolling 1680 patients with stroke and proximal intracranial LVO presenting within 24 hours of time last known to be well. Recruitment took place between February 9, 2022, and June 30, 2023, with a final follow-up on September 30, 2023.InterventionsEligible patients were randomly assigned to intravenous methylprednisolone (n = 839) at 2 mg/kg/d or placebo (n = 841) for 3 days adjunctive to endovascular thrombectomy. Main Outcomes and Measures The primary efficacy outcome was disability level at 90 days as measured by the overall distribution of the modified Rankin Scale scores (range, 0 [no symptoms] to 6 [death]). The primary safety outcomes included mortality at 90 days and the incidence of symptomatic intracranial hemorrhage within 48 hours. Results Among 1680 patients randomized (median age, 69 years; 727 female [43.3%]), 1673 (99.6%) completed the trial. The median 90-day modified Rankin Scale score was 3 (IQR, 1-5) in the methylprednisolone group vs 3 (IQR, 1-6) in the placebo group (adjusted generalized odds ratio for a lower level of disability, 1.10 [95% CI, 0.96-1.25]; P = .17). In the methylprednisolone group, there was a lower mortality rate (23.2% vs 28.5%; adjusted risk ratio, 0.84 [95% CI, 0.71-0.98]; P = .03) and a lower rate of symptomatic intracranial hemorrhage (8.6% vs 11.7%; adjusted risk ratio, 0.74 [95% CI, 0.55-0.99]; P = .04) compared with placebo. Conclusions and Relevance Among patients with acute ischemic stroke due to LVO undergoing endovascular thrombectomy, adjunctive methylprednisolone added to endovascular thrombectomy did not significantly improve the degree of overall disability.Trial RegistrationChiCTR.org.cn Identifier: ChiCTR210005172

Fizikalno-kemijska svojstva jestivih zaštitnih filmova dobivenih iz smjese kitozana, škroba manioke i želatine plastificirane glicerolom

Edible films from chitosan, cassava starch, and gelatin plasticized with glycerol have been developed by casting method, and the effects of cassava starch (50, 100 and 150 g per 100 g of chitosan), gelatin (0, 25 and 50 g per 100 g of chitosan) and glycerol (21, 42 and 63 g per 100 g of chitosan) from the film solution on various properties of chitosan-based films have been studied using response surface methodology (RSM). The possible interactions between the major components were evaluated by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The properties of the resulting chitosan-based blends for films were greatly influenced by the incorporation of cassava starch, gelatin and glycerol. The introduction of gelatin and gelatinized cassava starch suppressed the semicrystalline peaks of chitosan films. The amino peak of gelatin shifted from 1542 to 1559 cm^–1, and the NH and/or OH peak of gelatin, cassava starch and chitosan films shifted from 3384, 3414 and 3421, respectively, to 3422 cm^–1 in the composite film. These results indicate that there was an interaction and molecular miscibility among the major components. The growth inhibition of phytopathogen on mango fruit surface indicated the efficiency of these coatings and they can be applied for the conservation of fresh or minimally processed fruits and vegetables.Lijevanjem su dobiveni jestivi filmovi od kitozana, škroba manioke i želatine plastificirane glicerolom, a primjenom metode odzivnih površina ispitan je utjecaj masenog udjela škroba manioke (50, 100 i 150 g/100 g kitozana), želatine (0, 25 i 50 g/100 g kitozana) i glicerola (21, 42 i 63 g/100 g kitozana) na svojstva kompozitnih filmova. Moguće interakcije glavnih sastojaka ispitane su difrakcijom x-zraka i infracrvenom spektroskopijom s Fourierovom transformacijom. Svojstva kompozitnih filmova na bazi kitozana uvelike ovise o ugradnji škroba manioke, želatine i glicerola. Ugradnjom želatine i želatiniranog škroba manioke smanjila se visina odzivnih pikova semikristalastih polimera. Analizom kompozitnih filmova utvrđeno je da se pik aminoskupine u želatini premjestio s 1542 na 1559 cm^-1, a pikovi NH i/ili OH skupina u filmovima od želatine, škroba manioke i kitozana pomakli sa 3384, 3414 i 3421 na 3422 cm^-1. Dobiveni rezultati pokazuju da je došlo do uzajamnog djelovanja i miješanja molekula glavnih sastojaka filmova. Inhibicijom rasta fitopatogena na površini ploda manga dokazana je djelotvornost tako dobivenih prevlaka pri čuvanju svježeg ili minimalno prerađenog voća i povrća