Single-cell RNA analysis has been integrated with spatial protein profiling to create a single–cell type map of human tissues.

The prevalence of non‐alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l ‐serine, N ‐acetyl‐ l ‐cysteine (NAC), nicotinamide riboside (NR), and l ‐carnitine by performing a 7‐day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome‐scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long‐term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.

Lung adenocarcinoma (LUAD) is the one of the most common subtypes in lung cancer. Although various targeted therapies have been used in the clinical practice, the 5-year overall survival rate of patients is still low. Thus, it is urgent to identify new therapeutic targets and develop new drugs for the treatment of the LUAD patients. Survival analysis was used to identify the prognostic genes. Gene co-expression network analysis was used to identify the hub genes driving the tumor development. A profile-based drug repositioning approach was used to repurpose the potentially useful drugs for targeting the hub genes. MTT and LDH assay were used to measure the cell viability and drug cytotoxicity, respectively. Western blot was used to detect the expression of the proteins. We identified 341 consistent prognostic genes from two independent LUAD cohorts, whose high expression was associated with poor survival outcomes of patients. Among them, eight genes were identified as hub genes due to their high centrality in the key functional modules in the gene-co-expression network analysis and these genes were associated with the various hallmarks of cancer (e.g., DNA replication and cell cycle). We performed drug repositioning analysis for three of the eight genes (CDCA8, MCM6, and TTK) based on our drug repositioning approach. Finally, we repurposed five drugs for inhibiting the protein expression level of each target gene and validated the drug efficacy by performing in vitro experiments. We found the consensus targetable genes for the treatment of LUAD patients with different races and geographic characteristics. We also proved the feasibility of our drug repositioning approach for the development of new drugs for disease treatment.

Sarcopenia is a major public health concern among older adults, leading to disabilities, falls, fractures, and mortality. This study aimed to elucidate the pathophysiological mechanisms of sarcopenia and identify potential therapeutic targets using systems biology approaches. RNA-seq data from muscle biopsies of 24 sarcopenic and 29 healthy individuals from a previous cohort were analysed. Differential expression, gene set enrichment, gene co-expression network, and topology analyses were conducted to identify target genes implicated in sarcopenia pathogenesis, resulting in the selection of 6 hub genes (PDHX, AGL, SEMA6C, CASQ1, MYORG, and CCDC69). A drug repurposing approach was then employed to identify new pharmacological treatment options for sarcopenia (clofibric-acid, troglitazone, withaferin-a, palbociclib, MG-132, bortezomib). Finally, validation experiments in muscle cell line (C2C12) revealed MG-132 and troglitazone as promising candidates for sarcopenia treatment. Our approach, based on systems biology and drug repositioning, provides insight into the molecular mechanisms of sarcopenia and offers potential new treatment options using existing drugs.

Bu çalışmada Giresun ilinde yetişen yaban mersininin ( Vaccinium myrtillus ) meyve ve yaprağı, hem yaş hem de kurutulmuş halinin dört farklı çözücüdeki ekstraktları (etanol, aseton, su ve dietil eter) ayrı ayrı incelenmiştir. Bitkisel ürünlerin antioksidan kapasitelerini değerlendirmek için çeşitli yöntemler kullanılmıştır. Bu yöntemler, FRAP (Fe 3+ İndirgeme Antioksidan Gücü), DPPH● giderme ve toplam polifenol tayinini içermektedir. FRAP tayini yönünden, ekstraktların indirgeme güçlerinin aseton > etanol > su > dietil eter şeklinde sıralandığı görülmüştür. Serbest radikal giderme aktivitesi antioksidan sonuçlarına göre, kurutulmuş halde alınan örneklerin ekstraktları, yaş haline göre daha iyi düzeyde DPPH radikali giderme aktivitesi sergilemiştir ve en yüksek aktiviteyi çözücüsü etanol olan kuru yaprak ekstraktının gösterdiği bulunmuştur. Toplam fenolik madde miktarı tayinine göre ise, ekstraktlarda var olan fenolik madde içeriklerinin gallik asit eşdeğeri cinsinden 0.121±0.00-19.484±1.85 mg/g aralığında değiştiği ve en yüksek aktiviteyi yaban mersininin çözücüsü su olan kuru yaprak ekstraktının gösterdiği belirlenmiştir. Aynı zamanda bitki ekstrelerindeki antimikrobiyal aktivite, Agar disk difüzyon yöntemi kullanılarak tespit edilmiştir. Yaban mersini bitkisi ile hazırlanan ekstraktlar arasında, çözücüsü etanol ve aseton olan ekstrakların test mikroorganizmalarının çoğuna karşı iyi derecede aktivite gösterdiği bulunmuştur.