Research in Molecular Medicine
Volume:11 Issue: 3, Aug 2023

Alzheimer’s disease (AD), the most common neurodegenerative disorder, is characterized by the accumulation of amyloid-β (Aβ) plaques, leading to progressive cognitive decline. Targeting Aβ aggregation has become a major therapeutic focus, and peptide-based inhibitors have emerged as a promising approach due to their ability to specifically bind to Aβ and prevent its toxic oligomerization and fibril formation. This review discusses the advancements in Aβ-inhibiting peptides, including those derived from the Aβ sequence, as well as novel peptides discovered through phage display and mirror-image phage display technologies. These peptides offer significant advantages such as high selectivity and lower neurotoxicity, making them attractive candidates for therapeutic development. However, critical challenges—such as enzymatic degradation, poor blood-brain barrier (BBB) penetration, and the tendency for self-aggregation—have limited their clinical application. To overcome these barriers, recent innovations such as the incorporation of D-amino acids, cyclization, and retro-inverso modifications have improved peptide stability and bioavailability. Despite these improvements, further research is essential to optimize peptide design, enhance BBB permeability, and ensure long-term efficacy. This review emphasizes the importance of rational peptide design and the development of advanced delivery systems to address these limitations. By refining the molecular interactions and pharmacokinetic properties of Aβ-inhibiting peptides, future studies could significantly enhance their therapeutic potential. Ultimately, these efforts aim to advance peptide-based treatments through clinical trials and bring about meaningful progress in AD therapy.

Cholecystitis, inflammation of the gallbladder, has created a significant burden globally. The prevailing paradigm of awaiting irreversible damage before surgically removing the gallbladder is not only traumatic and risky but also fails to address the underlying causes. However, exponential growth in scientific insights now promises a shift towards precision prevention and cure.

Pathophysiological mechanisms involved in cystic duct obstruction by gallstones cause gallbladder stasis, direct mucosal injury, vascular compromise, leukocyte infiltration, and secondary infection. Advanced imaging, multiomics profiling, and machine learning unpack early molecular events in lithogenesis and inflammation missed by traditional techniques. Revolutionary endoluminal interventions, anti-inflammatory pharmaceuticals, antibiotic-eluting stents and medications targeting root lithogenic pathways offer alternatives to surgery for drainage restoration and stone prevention. Lifestyle optimization guided by nutrigenomics and pharmacogenomics increasingly personalizes risk factor modification. Ongoing exponential technological gains in nanomedicine, artificial intelligence integration, and minimally invasive techniques promise further preemptive, curative, non-surgical paradigms addressing pathogenesis at the molecular source.

Analysis revealed previously unidentified molecular signatures in early-stage cholecystitis, enabling intervention before irreversible damage occurs. Personalized risk factor modification guided by nutrigenomic and pharmacogenomic profiling demonstrated significant preventive potential. Integration of artificial intelligence with nanomedicine technologies showed promising results in predicting and preventing stone formation. Novel non-surgical interventions achieved 73% success in restoring drainage and preventing stone formation, with significantly lower complication rates compared to traditional cholecystectomy.

Synergizing breakthroughs across domains now position cholecystitis management for a monumental shift from reactive treatment on macroscopic changes towards proactive precision prevention, cure, and health maintenance by comprehending and controlling the underlying molecular cascades. This transformation promises dramatic improvements in patient safety, quality of life, mortality and healthcare economics.

The COVID-19 pandemic, caused by SARS-CoV-2, has presented a global health challenge. Older people and patients with underlying conditions such as hypertension, diabetes, and obesity are more susceptible to severe disease outcomes. Obesity or high body mass (BMI) index is a significant risk factor for creating diabetes and plays a crucial role in the pathogenesis of COVID-19 infection. Obesity has been shown to increase vulnerability to infections, making it a significant risk factor for COVID-19. This study aims to investigate the relationship between BMI and COVID-19 severity and outcomes in patients with and without diabetes.

This case-control study was conducted on 400 patients with confirmed COVID-19 infection, referred to teaching hospitals in Sari City, Iran, during April and May 2019. The study population consisted of 192 diabetic patients (case group) and 208 non-diabetic individuals (control group), matched for age and sex. Participants’ data, including demographics, medical history, laboratory findings, and disease progression details, were collected using a comprehensive questionnaire. According to CDC criteria, COVID-19 disease severity was defined as mild, moderate, and severe. The relationship between BMI and COVID-19 severity was compared between the diabetic and non-diabetic groups.

This study was conducted on 192 diabetic and 208 non-diabetic COVID-19 patients with an average age of 62.85±0.88 and 53.21±1.18 years, respectively. The average BMI in the diabetic group was 28.68±0.4, whereas it was 26.94±0.31 (P=0.001) in the non-diabetic group. There was a statistically significant difference in the severity of COVID-19 infection between diabetic and non-diabetic patients (P=0.008). The results showed a statistically significant difference in disease severity based on BMI in the diabetic group (P=0.02). Significant differences were observed in the need for mechanical ventilation (P=0.000) and mortality in people with diabetes compared to nondiabetics. A significant association was observed between BMI and ICU admission in both diabetic (P=0.001) and non-diabetic (P=0.000) groups.

The study concluded that BMI may be a significant risk factor for severe COVID-19 outcomes, particularly among people with diabetes. This finding emphasizes the importance of BMI in disease prevention and control strategies, especially for populations with underlying conditions like diabetes.

This research aims to investigate the performance of 8 weeks of aerobic exercise and vitamin D supplementation on nitric oxide (NO) and endothelin 1 (ET-1) indicators in patients with high blood pressure and vitamin D deficiency.

In this quasi-experimental research, 40 qualified men and women were randomly divided into four groups (supplement group, placebo + exercise group, supplement + exercise group, and control group). The training program of the experimental groups included 8 weeks of aerobic exercise running on a treadmill (3 sessions per week). Two groups (exercise + supplement and supplement group) received vitamin D supplement daily in the amount of 2000 international units in a double-blind manner, and the exercise + placebo group received a placebo capsule containing maltodextrin daily. Blood sampling was done to evaluate biochemical variables 48 hours before and after the intervention in a fasting state.

The research results show that after 8 weeks of aerobic training with vitamin D supplementation, there was no significant effect on body mass index, NO, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), vitamin D, and weight (P<0.05), but the effects were significant on ET-1 level and systolic blood pressure which changed in the supplement, supplement+exercise, and exercise+placebo groups compared to the control group (P<0.05). Also, the vitamin D increase showed a significant change (P<0.05).

Based on the results of the present study, taking vitamin D supplements for 8 weeks along with aerobic activity reduces ET-1, increases NO, and improves blood pressure in hypertensive people with vitamin D deficiencies.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen and a historically emerging zoonotic pathogen of public health and veterinary importance. It can cause severe chronic infections. The morbidity of MRSA infections has increased worldwide and is of great concern. Nevertheless, a change in treatment strategies, including the use of new antibiotics or combination therapy, is necessary for the treatment of this infection. The research investigated the synergistic effects of vancomycin and zinc oxide on MRSA and the viability of the lung cancer cell line A549 and the normal cell line BEAS.

In this study, the minimum inhibitory concentration (MIC) of zinc oxide nanoparticles (ZnO-NPs) and vancomycin was determined using the microdilution method. The fractional inhibitory concentration index (FICI) was calculated using the checkerboard method to evaluate the synergistic effect of ZnO-NPs and vancomycin. The effect of the combination of ZnO-NPs and vancomycin on the viability of lung cancer cell line A549 was also tested by MTT assay.

The MIC values showed that all isolates were sensitive to vancomycin with the exception ofexcept for one isolate with an MIC of ≤2 µg/mL. The synergistic effect of the combination of ZnO NPs and vancomycin was observed in two MRSA isolates and one MSSA strain using the checkerboard methodUsing the checkerboard method, the synergistic effect of the combination of ZnO-NPs and vancomycin was observed in two MRSA isolates and one MSSA strain. The combination of vancomycin and ZnO NPs caused less viability in the A549 lung cancer cell line (25.7%) than in BEAS (90%).

Combining vancomycin and ZnO-NPs at appropriate dosage intervals may be beneficial in treating MRSA. The combination of vancomycin and ZnO-NPs may also play a dual role in lung cancer patients with evidence of resistance to MRSA by reducing cancer cell survival.

Gastric cancer (GC) poses a significant health challenge worldwide. Recognizing its complex and diverse nature, the cancer genome atlas (TCGA) research network has identified four distinct subtypes of GC. Among these subtypes, Epstein-Barr virus (EBV) associated GC accounts for around 9% of all GC cases. The primary aim of this study was to identify dysregulated genes in EBV-positive samples in contrast to EBV-negative samples, with the secondary goal of assessing their potential utility as diagnostic biomarkers. In addition, the study also aimed to evaluate the correlation between the expression levels of these candidate genes and drug resistance and sensitivity.

Differential gene expression analysis was employed to compare gene expression patterns between the EBV-positive and EBV-negative groups within the TCGA-stomach adenocarcinoma (TCGA-STAD) cohort. Gene ontology (GO) analyses were performed to elucidate the biological roles of the candidate genes. GSE13861 was used to confirm the gene expression levels in GC samples compared to the normal samples.

Our findings revealed that 128 genes exhibited up-regulation in EBV-positive samples compared to EBV-negative samples. CCL1, CCL5, CXCL1, CXCL10, CXCL11, KLRK1, and TBX21 genes were notably enriched in the process of leukocyte migration, which emerged as the hub pathway with the highest degree of interactions among the identified terms. Our analysis indicated that most of these genes could be deemed potential diagnostic biomarkers, as their area under the curve values exceeded 0.9. Additionally, our results demonstrated a correlation between some of these genes and resistance to specific drugs, including panobinostat, L-685458, L-BW242, and sorafenib.

Our study identified several key genes closely linked to EBV status and demonstrated a strong association with drug resistance. These genes hold promise as molecular markers for predicting EBV-positive samples.