Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Bacillus Subtilis-Fermented White Sword Bean Extract on Adipogenesis and Lipolysis of 3T3-L1 Adipocytes

To investigate the adipogenesis and lipolysis effects of the Bacillus subtilis-fermented white sword bean extract (FWSBE) on 3T3-L1 adipocytes, we treated 3T3-L1 preadipocytes before and after differentiation with FWSBE and measured triglyceride, free glycerol, mRNA, and protein levels. First, FWSBE reduced the cell viability of 3T3-L1 pre-adipocytes under 1000 µg/mL conditions. Triglyceride accumulation in 3T3-L1 pre-adipocytes was suppressed, and free glycerol content in mature 3T3-L1 adipocytes was increased in the FWSBE treatment groups, indicating that FWSBE has anti-obesity effects. Further, FWSBE suppressed adipogenesis in 3T3-L1 pre-adipocytes by lowering the protein levels of C/EBPα, PPARγ, and FAS and increasing the level of pACC and pAMPK. Additionally, FWSBE promoted lipolysis in mature 3T3-L1 adipocytes by increasing the transcription levels of Ppara, Acox, and Lcad and the protein levels of pHSL and ATGL. Thus, we suggest that FWSBE can be a potential dietary supplement because of its anti-obesity properties.
HO-1 Modulates Aerobic Glycolysis through LDH in Prostate Cancer Cells

Prostate cancer (PCa) is the second most diagnosed malignancy and the fifth leading cause of cancer associated death in men worldwide. Dysregulation of cellular energetics has become a hallmark of cancer, evidenced by numerous connections between signaling pathways that include oncoproteins and key metabolic enzymes. We previously showed that heme oxygenase 1 (HO-1), a cellular homeostatic regulator counteracting oxidative and inflammatory damage, exhibits anti-tumoral activity in PCa cells, inhibiting cell proliferation, migration, tumor growth and angiogenesis. The aim of this study was to assess the role of HO-1 on the metabolic signature of PCa. After HO-1 pharmacological induction with hemin, PC3 and C4-2B cells exhibited a significantly impaired cellular metabolic rate, reflected by glucose uptake, ATP production, lactate dehydrogenase (LDH) activity and extracellular lactate levels. Further, we undertook a bioinformatics approach to assess the clinical significance of LDHA, LDHB and HMOX1 in PCa, identifying that high LDHA or low LDHB expression was associated with reduced relapse free survival (RFS). Interestingly, the shortest RFS was observed for PCa patients with low HMOX1 and high LDHA, while an improved prognosis was observed for those with high HMOX1 and LDHB. Thus, HO-1 induction causes a shift in the cellular metabolic profile of PCa, leading to a less aggressive phenotype of the disease.
Endothelial Dysfunction and Cardiovascular Disease: History and Analysis of the Clinical Utility of the Relationship

The endothelium is the single-cell monolayer that lines the entire vasculature. The endothelium has a barrier function to separate blood from organs and tissues but also has an increasingly appreciated role in anti-coagulation, vascular senescence, endocrine secretion, suppression of inflammation and beyond. In modern times, endothelial cells have been identified as the source of major endocrine and vaso-regulatory factors principally the dissolved lipophilic vosodilating gas, nitric oxide and the potent vascular constricting G protein receptor agonists, the peptide endothelin. The role of the endothelium can be conveniently conceptualized. Continued investigations of the mechanism of endothelial dysfunction will lead to novel therapies for cardiovascular disease. In this review, we discuss the impact of endothelial dysfunction on cardiovascular disease and assess the clinical relevance of endothelial dysfunction.
Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein

Accumulation of α-Synuclein (αSyn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson′s disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53–87 amino acid residues of human αSyn by recombinant adeno associated viral vector (AAV-NAC32) downregulated αSyn protein in SH-SY5Y cells and rat brain. This study characterizes the behavioral phenotype and dopaminergic protection in animals receiving AAV-NAC32. Our results show that adult DAT-Cre rats selectively overexpress αSyn in nigra dopaminergic neurons after local administration of AAV-DIO-αSyn. These animals develop PD-like phenotype, including bradykinesia and loss of tyrosine hydroxylase (TH) immunoreactivity in substantia nigra pars compacta dorsal tier (SNcd). An injection of AAV-NAC32 to nigra produces a selective antibody against αSyn and normalizes the behavior. AAV-NAC32 significantly increases TH, while reduces αSyn immunoreactivity in SNcd. Altogether, our data suggest that an AAV-mediated gene transfer of NAC32 antibody effectively antagonizes αSyn-mediated dopaminergic degeneration in nigra, which may be a promising therapeutic candidate for synucleinopathy or PD.
Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury

Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl4) to induce chronic liver injury. Eritoran (10 mg/kg) or a vehicle was randomly intraperitoneally administered to the FFD-fed mice and the CCl4-injured mice. Primary mouse liver cells were cultured with lipopolysaccharide (LPS) or eritoran. In both FFD and CCl4 mouse models, eritoran significantly reduced serum ALT levels and decreased hepatic inflammatory cell infiltration without altering hepatic steatosis. Additionally, eritoran attenuated liver fibrosis by decreasing hepatic stellate cells (HSCs) activation and the abundance of α-smooth muscle actin and transforming growth factor-β1. Hepatic TLR4 downstream signaling including MyD88 expression, NF-κB p65 nuclear translocation, p38 and JNK phosphorylation were successfully inhibited by eritoran. In the in vitro study, LPS-induced nuclear translocation of NF-κB in primary HSCs and Kupffer cells was significantly suppressed by eritoran. In conclusion, eritoran attenuated hepatic inflammation and fibrosis by inhibition of the TLR4 signaling pathway in mice with chronic liver injury. Eritoran may serve as a potential drug for chronic liver disease.
Stride Length Predicts Adverse Clinical Events in Older Adults: A Systematic Review and Meta-Analysis

Background: This meta-analysis aims to estimate the power of walking stride length as a predictor of adverse clinical events in older adults. Methods: We searched all electronic databases until April 2021 for studies reporting stride length and other spatial gait parameters, including stride velocity, stride width, step width and stride variability, and compared them with clinical outcomes in the elderly. Meta-analyses of odds ratios (ORs) of effects of stride length on clinical outcomes used the generic inverse variance method and random model effects. Clinical outcomes were major adverse events (MAEs), physical disability and mortality. Results: Eleven cohort studies with 14,167 patients (mean age 75.4 ± 5.6 years, 55.8% female) were included in the analysis. At 33.05 months follow up, 3839 (27%) patients had clinical adverse events. Baseline stride length was shorter, WMD −0.15 (−0.19 to −0.11, p < 0.001), and stride length variability was higher, WMD 0.67 (0.33 to 1.01, p < 0.001), in fallers compared to non-fallers. Other gait parameters were not different between the two groups (p > 0.05 for all). Short stride length predicted MAE OR 1.36 (95% CI; 1.19 to 1.55, p < 0.001), physical disability OR 1.26 (95% CI; 1.11 to 1.44, p = 0.004) and mortality OR 1.69 (95% CI; 1.41 to 2.02, p < 0.001). A baseline normalized stride length ≤ 0.64 m was more accurate in predicting adverse clinical events, with summary sensitivity 65% (58–71%), specificity 72% (69–75%) and accuracy 75.5% (74.2–76.7%) compared to stride length variability 5.7%, with summary sensitivity 66% (61–70%), specificity 56% (54–58%) and accuracy 57.1% (55.5–58.6%). Conclusion: The results of this meta-analyses support the significant value of stride length for predicting life-threatening clinical events in older adults. A short stride length of ≤0.64 m accurately predicted clinical events, over and above other gait measures.
The Prevalence of TET2 Gene Mutations in Patients with BCR-ABL-Negative Myeloproliferative Neoplasms (MPN): A Systematic Review and Meta-Analysis

Simple Summary Many molecular biology techniques have been widely used to study the pathogenesis of different diseases, particularly haematologic malignancies which are generally caused by abnormalities in the genome. TET2 gene is one of the commonly found mutated genes in BCR-ABL-negative myeloproliferative neoplasms. However, the prevalence of TET2 gene mutations in the disease remains unclear. Therefore, this study aims to estimate the prevalence of TET2 gene mutations in myeloproliferative neoplasms. The findings may be helpful for future research, diagnoses and the identification of better therapeutic strategies to manage the diseases. Abstract Multiple recurrent somatic mutations have recently been identified in association with myeloproliferative neoplasms (MPN). This meta-analysis aims to assess the pooled prevalence of TET2 gene mutations among patients with MPN. Six databases (PubMed, Scopus, ScienceDirect, Google Scholar, Web of Science and Embase) were searched for relevant studies from inception till September 2020, without language restrictions. The eligibility criteria included BCR-ABL-negative MPN adults with TET2 gene mutations. A random-effects model was used to estimate the pooled prevalence with 95% confidence intervals (CIs). Subgroup analyses explored results among different continents and countries, WHO diagnostic criteria, screening methods and types of MF. Quality assessment was undertaken using the Joanna Briggs Institute critical appraisal tool. The study was registered with PROSPERO (CRD42020212223). Thirty-five studies were included (n = 5121, 47.1% female). Overall, the pooled prevalence of TET2 gene mutations in MPN patients was 15.5% (95% CI: 12.1–19.0%, I2 = 94%). Regional differences explained a substantial amount of heterogeneity. The prevalence of TET2 gene mutations among the three subtypes PV, ET and MF were 16.8%, 9.8% and 15.7%, respectively. The quality of the included studies was determined to be moderate–high among 83% of the included studies. Among patients with BCR-ABL-negative MPN, the overall prevalence of TET2 gene mutations was 15.5%.
Mesenchymal Stem Cells Engineered by Nonviral Vectors: A Powerful Tool in Cancer Gene Therapy

Due to their “tumor homing” and “immune privilege” characteristics, the use of mesenchymal stem cells (MSCs) has been proposed as a novel tool against cancer. MSCs are genetically engineered in vitro and then utilized to deliver tumoricidal agents, including prodrugs and bioactive molecules, to tumors. The genetic modification of MSCs can be achieved by various vectors, and in most cases viral vectors are used; however, viruses may be associated with carcinogenesis and immunogenicity, restricting their clinical translational potential. As such, nonviral vectors have emerged as a potential solution to address these limitations and have gradually attracted increasing attention. In this review, we briefly revisit the current knowledge about MSC-based cancer gene therapy. Then, we summarize the advantages and challenges of nonviral vectors for MSC transfection. Finally, we discuss recent advances in the development of new nonviral vectors, which have provided promising strategies to overcome obstacles in the gene modulation of MSCs.
Action Mechanisms of Curcumin in Alzheimer’s Disease and Its Brain Targeted Delivery

AD is a chronic neurodegenerative disease. Many different signaling pathways, such as Wnt/β-catenin, Notch, ROS/JNK, and PI3K/Akt/mTOR are involved in Alzheimer’s disease and crosstalk between themselves. A promising treatment involves the uses of flavonoids, and one of the most promising is curcumin; however, because it has difficulty permeating the blood–brain barrier (BBB), it must be encapsulated by a drug carrier. Some of the most frequently studied are lipid nanocarriers, liposomes, micelles and PLGA. These carriers are further conjugated with brain-targeting agents such as lactoferrin and transferrin. In this review paper, curcumin and its therapeutic effects, which have been examined in vivo, are analyzed and then the delivery systems to the brain are addressed. Overall, the analysis of the literature revealed great potential for curcumin in treating AD and indicated the challenges that require further research.
Stem Cells as a Source of Pancreatic Cells for Production of 3D Bioprinted Bionic Pancreas in the Treatment of Type 1 Diabetes

Type 1 diabetes (T1D) is the third most common autoimmune disease which develops due to genetic and environmental risk factors. Often, intensive insulin therapy is insufficient, and patients require a pancreas or pancreatic islets transplant. However, both solutions are associated with many possible complications, including graft rejection. The best approach seems to be a donor-independent T1D treatment strategy based on human stem cells cultured in vitro and differentiated into insulin and glucagon-producing cells (β and α cells, respectively). Both types of cells can then be incorporated into the bio-ink used for 3D printing of the bionic pancreas, which can be transplanted into T1D patients to restore glucose homeostasis. The aim of this review is to summarize current knowledge about stem cells sources and their transformation into key pancreatic cells. Last, but not least, we comment on possible solutions of post-transplant immune response triggered stem cell-derived pancreatic cells and their potential control mechanisms.
Levels of Circulating PD-L1 Are Decreased in Patients with Resectable Cholangiocarcinoma

Tumor resection represents the only curative treatment option for patients with biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (CCA), perihilar and extrahepatic CCA and gallbladder cancer. However, many patients develop early tumor recurrence and are unlikely to benefit from surgery. Therefore, markers to identify ideal surgical candidates are urgently needed. Circulating programmed cell death 1 ligand 1 (PD-L1) has recently been associated with different malignancies, including pancreatic cancer which closely resembles BTC in terms of patients’ prognosis and tumor biology. Here, we aim at evaluating a potential role of circulating PD-L1 as a novel biomarker for resectable BTC. Methods: Serum levels of PD-L1 were analyzed by ELISA in 73 BTC patients and 42 healthy controls. Results: Circulating levels of preoperative PD-L1 were significantly lower in patients with BTC compared to controls. Patients with low PD-L1 levels displayed a strong trend towards an impaired prognosis, and circulating PD-L1 was negatively correlated with experimental markers of promalignant tumor characteristics such as CCL1, CCL21, CCL25 and CCL26. For 37 out of 73 patients, postoperative PD-L1 levels were available. Interestingly, after tumor resection, circulating PD-L1 raised to almost normal levels. Notably, patients with further decreasing PD-L1 concentrations after surgery showed a trend towards an impaired postoperative outcome. Conclusion: Circulating PD-L1 levels were decreased in patients with resectable BTC. Lack of normalization of PD-L1 levels after surgery might identify patients at high risk for tumor recurrence or adverse outcome.
The Epic of In Vitro Meat Production—A Fiction into Reality

Due to a proportionally increasing population and food demands, the food industry has come up with wide innovations, opportunities, and possibilities to manufacture meat under in vitro conditions. The amalgamation of cell culture and tissue engineering has been the base idea for the development of the synthetic meat, and this has been proposed to be a pivotal study for a futuristic muscle development program in the medical field. With improved microbial and chemical advancements, in vitro meat matched the conventional meat and is proposed to be eco-friendly, healthy, nutrient rich, and ethical. Despite the success, there are several challenges associated with the utilization of materials in synthetic meat manufacture, which demands regulatory and safety assessment systems to manage the risks associated with the production of cultured meat. The role of 3D bioprinting meat analogues enables a better nutritional profile and sensorial values. The integration of nanosensors in the bioprocess of culture meat eased the quality assessment throughout the food supply chain and management. Multidisciplinary approaches such as mathematical modelling, computer fluid dynamics, and biophotonics coupled with tissue engineering will be promising aspects to envisage the future prospective of this technology and make it available to the public at economically feasible rates.
The Timecourses of Functional, Morphological, and Molecular Changes Triggered by Light Exposure in Sprague–Dawley Rat Retinas

Retinal neurodegeneration can impair visual perception at different levels, involving not only photoreceptors, which are the most metabolically active cells, but also the inner retina. Compensatory mechanisms may hide the first signs of these impairments and reduce the likelihood of receiving timely treatments. Therefore, it is essential to characterize the early critical steps in the neurodegenerative progression to design adequate therapies. This paper describes and correlates early morphological and biochemical changes in the degenerating retina with in vivo functional analysis of retinal activity and investigates the progression of neurodegenerative stages for up to 7 months. For these purposes, Sprague–Dawley rats were exposed to 1000 lux light either for different durations (12 h to 24 h) and examined seven days afterward (7d) or for a fixed duration (24 h) and monitored at various time points following the exposure (up to 210d). Flash electroretinogram (fERG) recordings were correlated with morphological and histological analyses to evaluate outer and inner retinal disruptions, gliosis, trophic factor release, and microglial activation. Twelve hours or fifteen hours of exposure to constant light led to a severe retinal dysfunction with only minor morphological changes. Therefore, early pathological signs might be hidden by compensatory mechanisms that silence retinal dysfunction, accounting for the discrepancy between photoreceptor loss and retinal functional output. The long-term analysis showed a transient functional recovery, maximum at 45 days, despite a progressive loss of photoreceptors and coincident increases in glial fibrillary acidic protein (GFAP) and basic fibroblast growth factor-2 (bFGF-2) expression. Interestingly, the progression of the disease presented different patterns in the dorsal and ventral retina. The information acquired gives us the potential to develop a specific diagnostic tool to monitor the disease’s progression and treatment efficacy.
Cleaning the Medicago Microarray Database to Improve Gene Function Analysis

Transcriptomics studies have been facilitated by the development of microarray and RNA-Seq technologies, with thousands of expression datasets available for many species. However, the quality of data can be highly variable, making the combined analysis of different datasets difficult and unreliable. Most of the microarray data for Medicago truncatula, the barrel medic, have been stored and made publicly accessible on the web database Medicago truncatula Gene Expression atlas (MtGEA). The aim of this work is to ameliorate the quality of the MtGEA database through a general method based on logical and statistical relationships among parameters and conditions. The initial 716 columns available in the dataset were reduced to 607 by evaluating the quality of data through the sum of the expression levels over the entire transcriptome probes and Pearson correlation among hybridizations. The reduced dataset shows great improvements in the consistency of the data, with a reduction in both false positives and false negatives resulting from Pearson correlation and GO enrichment analysis among genes. The approach we used is of general validity and our intent is to extend the analysis to other plant microarray databases.
Chemical Extraction and Gastrointestinal Digestion of Honey: Influence on Its Antioxidant, Antimicrobial and Anti-Inflammatory Activities

The effect of chemical extraction and in vitro digestion of different kinds of honey on bioactive compounds (total phenolic compounds and flavonoids) and biological activities (antioxidant, antimicrobial and anti-inflammatory) was investigated. The antioxidant activity was evaluated against three radicals (ABTS•+, ROO•, •OH), and the antimicrobial activity was studied against five bacteria (Staphylococcus aureus, Listeria monocytogenes, Escherichia coli, Streptococcus mutans and Pseudomona aeruginosa) and one yeast (Candida albicans). The results show that in comparison with raw honeys, the methanolic extracts exhibited lower values for phenols, flavonoids and antioxidant activity and higher anti-inflammatory and antimicrobial activities against L. monocytogenes. The higher anti-inflammatory activity indicates a possible use of dried honey extracts in the pharmaceutical and cosmetic industries. The digested honeys showed higher total phenolics and higher antioxidant activity than the pre-digested honeys, as well as higher antimicrobial activity against S. aureus and L. monocytogenes, which underlines the possible antioxidant and antimicrobial effects of honey in the human body after the digestion process.
The Impact of Elongation on Change in Electrical Resistance of Electrically Conductive Yarns Woven into Fabric

Electrically conductive yarns (ECYs) are gaining increasing applications in woven textile materials, especially in woven sensors suitable for incorporation into clothing. In this paper, the effect of the yarn count of ECYs woven into fabric on values of electrical resistance is analyzed. We also observe how the direction of action of elongation force, considering the position of the woven ECY, effects the change in the electrical resistance of the electrically conductive fabric. The measurements were performed on nine different samples of fabric in a plain weave, into which were woven ECYs with three different yarn counts and three different directions. Relationship curves between values of elongation forces and elongation to break, as well as relationship curves between values of electrical resistance of fabrics with ECYs and elongation, were experimentally obtained. An analytical mathematical model was also established, and analysis was conducted, which determined the models of function of connection between force and elongation, and between electrical resistance and elongation. The connection between the measurement results and the mathematical model was confirmed. The connection between the mathematical model and the experimental results enables the design of ECY properties in woven materials, especially textile force and elongation sensors.