Background: Distractor efficiency (DE) of multiple-choice questions (MCQs) responses is a component of the psychometric analysis used by the examiners to evaluate the distractors’ credibility and functionality. This study was conducted to evaluate the impact of the DE on the difficulty and discrimination indices. Methods: This cross-sectional study was conducted from April to June 2023. It utilizes the final exam of the Principles of Diseases Course with 45 s-year students. The exam consisted of 60 type A MCQs. Item analysis (IA) was generated to evaluate KR20, difficulty index (DIF), discrimination index (DIS), and distractor efficiency (DE). DIF was calculated as the percentage of examinees who scored the item correctly. DIS is an item’s ability to discriminate between higher and lower 27% of examinees. For DE, any distractor selected by less than 5% is considered nonfunctional, and items were classified according to the non-functional distractors. The correlation and significance of variance between DIF, DI, and DE were evaluated. Results: The total number of examinees was 45. The KR-20 of the exam was 0.91. The mean (M), and standard deviation (SD) of the DIF of the exam was 37.5(19.1), and the majority (69.5%) were of acceptable difficulty. The M (SD) of the DIS was 0.46 (0.22), which is excellent. Most items were excellent in discrimination (69.5%), only two were not discriminating (13.6%), and the rest were of acceptable power (16.9%). Items with excellent and good efficiency represent 37.3% each, while only 3.4% were of poor efficiency. The correlation between DE and DIF (p = 0.000, r= -0.548) indicates that items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and vice versa. The correlation between DE and DIS is significantly negative (P = 0.0476, r=-0.259). In such a correlation, items with efficient distractors are associated with low-discriminating items. Conclusions: There is a significant moderate negative correlation between DE and DIF (P = 0.00, r = -0.548) and a significant weak negative correlation between DE and DIS (P = 0.0476, r = -0.259). DIF has a non-significant negative correlation with DIS (P = 0.7124, r = -0.0492). DE impacts both DIF and DIS. Items with efficient distractors (low number of NFD) are associated with those having a low difficulty index (difficult items) and discriminating items. Improving the quality of DE will decrease the number of NFDs and result in items with acceptable levels of difficulty index and discrimination power.

Ulcerative colitis (UC) is a chronic relapsing inflammatory disease of the colorectal area that demonstrates a dramatically increasing incidence worldwide. This study provides novel insights into the capacity of the exogenous β-hydroxybutyrate and ketogenic diet (KD) consumption to alleviate dextran sodium sulfate (DSS)-induced UC in rats. Remarkably, both interventions attenuated disease activity and colon weight-to-length ratio, and improved macro and microstructures of the damaged colon. Importantly, both β-hydroxybutyrate and KD curbed the DSS-induced aberrant NLRP3 inflammasome activation as observed in mRNA and protein expression analysis. Additionally, inhibition of the NLRP3/NGSDMD-mediated pyroptosis was detected in response to both regimens. In parallel, these modalities attenuated caspase-1 and its associated consequences of IL-1β and IL-18 overproduction. They also mitigated apoptosis as indicated by the inactivation of caspase-3. The anti-inflammatory effects of BHB and KD were confirmed by the reported decline in the levels of inflammatory markers including MPO, NFκB, IL-6, and TNF-α. Moreover, these interventions exhibited antioxidative properties by reducing ROS production and improving antioxidative enzymes. Their effectiveness in mitigating UC was also evident in the renovation of normal intestinal epithelial barrier function, as shown by correcting the discrepancies in the levels of tight junction proteins ZO-1, OCLN, and CLDN5. Furthermore, their effects on the intestinal microbiota homeostasis were investigated. In terms of autophagy, exogenous β-hydroxybutyrate upregulated BECN-1 and downregulated p62, which may account for its superiority over KD in attenuating colonic damage. In conclusion, this study provides experimental evidence supporting the potential therapeutic use of β-hydroxybutyrate or β-hydroxybutyrate-boosting regimens in UC.

Idiopathic pulmonary fibrosis (IPF) is an irreversible and life-threatening lung disease of unknown etiology presenting only a few treatment options. TGF-β signaling orchestrates a cascade of events driving pulmonary fibrosis (PF). Notably, recent research has affirmed the augmentation of TGF-β receptor (TβR) signaling via HSP90 activation. HSP90, a molecular chaperone, adeptly stabilizes and folds TβRs, thus intricately regulating TGF-β1 signaling. Our investigation illuminated the impact of alvespimycin, an HSP90 inhibitor, on TGF-β-mediated transcriptional responses by inducing destabilization of TβRs. This outcome stems from the explicit interaction of TβR subtypes I and II with HSP90, where they are clients of this cellular chaperone. It is worth noting that regulation of proteasome-dependent degradation of TβRs is a critical standpoint in the termination of TGF-β signal transduction. Oleuropein, the principal bioactive compound found in Olea europaea, is acknowledged for its role as a proteasome activator. In this study, our aim was to explore the efficacy of a combined therapy involving oleuropein and alvespimycin for the treatment of PF. We employed a PF rat model that was induced by intratracheal bleomycin infusion. The application of this dual therapy yielded a noteworthy impediment to the undesired activation of TGF-β/mothers against decapentaplegic homologs 2 and 3 (SMAD2/3) signaling. Consequently, this novel combination showcased improvements in both lung tissue structure and function while also effectively restraining key fibrosis markers such as PDGF-BB, TIMP-1, ACTA2, col1a1, and hydroxyproline. On a mechanistic level, our findings unveiled that the antifibrotic impact of this combination therapy likely stemmed from the enhanced degradation of both TβRI and TβRII. In conclusion, the utilization of proteasomal activators in conjunction with HSP90 inhibitors ushers in a promising frontier for the management of PF.

Idiopathic pulmonary fibrosis is a fatal lung disorder in which the etiology and pathogenesis are still unobvious. Effective treatments are urgently needed considering that lung transplantation is the only treatment that could improve outcomes. This study aimed to investigate the therapeutic significance of the dual administration of pimitespib, an HSP90 inhibitor, and nifuroxazide, a STAT3 inhibitor, against bleomycin-induced pulmonary fibrosis in rats. Our results revealed that pimitespib/nifuroxazide inhibited bleomycin-induced alterations in the structure and the function of the lungs. They demonstrated significant decreases in the BALF total and differential cell counts, LDH activity, and total protein. Concurrently, there was a reduction in the accumulation of collagen as proved by decreased hydroxyproline and the gene expression of COL1A1 accompanied by lower levels of PDGF-BB, TIMP-1, and TGF-β. The levels of IL-6 were also downregulated. Pimitespib-induced inhibition of HSP90 led to subsequent inhibition of HIF-1α and STAT3 client proteins since the closed HSP90 would not enclose its client proteins. Therefore, pimitespib resulted in the repression of HIF-1α/CREB-p300 HAT as well as the STAT3/CREB-p300 HAT nuclear interactions. On the other hand, nifuroxazide resulted in a notable decline in pSTAT3 and HIF-1α levels. Subsequently, the combined effects of both drugs led to a substantial reduction in ECM deposition. Herein, pimitespib augmented nifuroxazide-induced disruption in the IL-6/STAT3/HIF-1α autocrine loop. Our findings also disclose that this novel loop is a promising therapeutic attack site for possible pulmonary fibrosis repression studies. Therefore, the use of pimitespib/nifuroxazide embodies an evolutionary perspective in managing pulmonary fibrosis.

Sorafenib, a multikinase inhibitor, is a first-line treatment for advanced hepatocellular carcinoma, but its long-term effectiveness is limited by the emergence of resistance mechanisms. One such mechanism is the reduction of microvessel density and intratumoral hypoxia caused by prolonged sorafenib treatment. Our research has demonstrated that HSP90 plays a critical role in conferring resistance to sorafenib in HepG2 cells under hypoxic conditions and N-Nitrosodiethylamine-exposed mice as well. This occurs through the inhibition of necroptosis on the one hand and the stabilization of HIF-1α on the other hand. To augment the effects of sorafenib, we investigated the use of ganetespib, an HSP90 inhibitor. We found that ganetespib activated necroptosis and destabilized HIF-1α under hypoxia, thus enhancing the effectiveness of sorafenib. Additionally, we discovered that LAMP2 aids in the degradation of MLKL, which is the mediator of necroptosis, through the chaperone-mediated autophagy pathway. Interestingly, we observed a significant negative correlation between LAMP2 and MLKL. These effects resulted in a reduction in the number of surface nodules and liver index, indicating a regression in tumor production rates in mice with HCC. Furthermore, AFP levels decreased. Combining ganetespib with sorafenib showed a synergistic cytotoxic effect and resulted in the accumulation of p62 and inhibition of macroautophagy. These findings suggest that the combined therapy of ganetespib and sorafenib may offer a promising approach for the treatment of hepatocellular carcinoma by activating necroptosis, inhibiting macroautophagy, and exhibiting a potential antiangiogenic effect. Overall, continued research is critical to establish the full therapeutic potential of this combination therapy.

The human oral microbiome is a complex, dynamic ecosystem critically involved in maintaining oral health and contributing to systemic well-being. Many bacteria and fungi are involved in oral cavities such as Penicillium , Rhodotorula , Saccharomycetales , Streptococcus , Veillonella , Neisseria , Actinomyces , and Schizophyllum. Disruption of microbial homeostasis, or dysbiosis, underpins a wide spectrum of oral diseases, including dental caries, periodontal disease, endodontic infections, and mucosal conditions. Recent advances in microbiome research have elucidated the mechanisms by which pathogenic microbial consortia, such as the red complex ( Porphyromonas gingivalis , Tannerella. forsythia , and Treponema denticola ), synergistically promote disease progression through virulence factors, metabolic interactions, and biofilm formation. Emerging microbiome-based therapies, comprising probiotics, postbiotics, predatory bacteria, and using bacteriophages, offer promising adjuncts or alternatives to traditional antimicrobial approaches by restoring microbial balance, reducing pathogenic load, and modulating host immune responses. For instance, probiotic strains like  Streptococcus salivarius and Lactobacillus spp. have demonstrated efficacy in reducing plaque, gingival inflammation, and pathogenic bacteria, as well as having significant immunological modulation, while postbiotics provide similar benefits with enhanced safety and stability. Additionally, predatory bacteria such as  Bdellovibrio bacteriovorus  show potential for selective bacterial elimination and combating periodontal diseases that are driven by Gram-negative anaerobes. Bacteriophages offer another precision tool for targeting oral pathogens by lysing bacteria upon replication. Finally, oral microbiota transplantation aimed at treating periodontal disease by restoring a balanced microbial community in the oral cavity. These innovative strategies, combined with a nuanced understanding of biofilm dynamics and host–microbe interactions, pave the way for personalized and ecologically sustainable oral health interventions. Continued research is essential to translate these promising approaches into clinical practice, optimize delivery systems, and elucidate long-term safety and efficacy.