Acute effects of photobiomodulation applied on the dorsal root ganglion in gout model-induced rats.

Gouty arthritis is an inflammatory disease that triggers symptoms such as pain, swelling, and joint stiffness. Since its main therapy is medication, research on other forms of treatment that do not generate side effects is necessary. Given this, the objective of this research was to evaluate the effects of combined photobiomodulation (LASER and LED) applied on the dorsal root ganglion (DRG) in an experimental model of gouty arthritis. For this, 40 Wistar rats were randomized into 4 groups: simulation of the model with saline injection, without treatment (CTL; n = 10); gout simulation with photobiomodulation treatment (CTL-PBM; n = 10); gout model with the injection of monosodium urate crystals (1.25 mg) in the femorotibial joint, without treatment (GOT; n = 10); or gout model with photobiomodulation treatment (GOT-PBM; n = 10). After 7 h of gout induction, photobiomodulation was performed with a cluster of 4 diodes applied to the GRD region in animals from the CTL-PBM and GOT-PBM groups. After analysing the results, it was concluded that the therapy favored the reduction of edema and joint incapacity, as well as the increase in the nociceptive threshold and plantar grip strength. Furthermore, PBM stimulated an increase in the inflammatory response (with increased levels of IL-1ß and greater recruitment of leukocytes) and greater activation of the antioxidant system. Therefore, PBM can be considered an effective therapeutic alternative to improve the functional status in this model of joint disease.

Exploring COVID-19 pathogenesis on command-line: A bioinformatics pipeline for handling and integrating omics data.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in late 2019 in Wuhan, China, and has proven to be highly pathogenic, making it a global public health threat. The immediate need to understand the mechanisms and impact of the virus made omics techniques stand out, as they can offer a holistic and comprehensive view of thousands of molecules in a single experiment. Mastering bioinformatics tools to process, analyze, integrate, and interpret omics data is a powerful knowledge to enrich results. We present a robust and open access computational pipeline for extracting information from quantitative proteomics and transcriptomics public data. We present the entire pipeline from raw data to differentially expressed genes. We explore processes and pathways related to mapped transcripts and proteins. A pipeline is presented to integrate and compare proteomics and transcriptomics data using also packages available in the Bioconductor and providing the codes used. Cholesterol metabolism, immune system activity, ECM, and proteasomal degradation pathways increased in infected patients. Leukocyte activation profile was overrepresented in both proteomics and transcriptomics data. Finally, we found a panel of proteins and transcripts regulated in the same direction in the lung transcriptome and plasma proteome that distinguish healthy and infected individuals. This panel of markers was confirmed in another cohort of patients, thus validating the robustness and functionality of the tools presented.

Effect of different selenium sources and concentrations on glutathione peroxidase activity and cholesterol metabolism of beef cattle.

The objective of this study was to investigate the effects of different Se sources and concentrations on glutathione forms and cholesterol metabolism in beef cattle. Sixty-three Nellore bulls (412 ± 19 kg body weight (BW); 24 mo old) were randomly assigned to a completely randomized design in a 2 × 3 + 1 factorial arrangement (63 pens; one animal/pen) with two Se sources (sodium selenite, ING and Se-yeast, ORG), three concentrations (0.3, 0.9, and 2.7 mg supplemental Se/kg dry matter (DM)), and control treatment (without Se supplementation) fed for 90 d. Blood samples were collected on day 0, 28, 56, and 84. Muscle and liver samples were collected at harvest. Hepatic GSSG (P = 0.004), GSH/GSSG ratio (P = 0.030), and GSH-Px (P = 0.004) were affected by Se source × concentration interaction. Oxidized glutathione was higher in the ORG group vs. ING at concentration 2.7 mg supplemental Se/kg DM, but at 0.3 mg supplemental Se/kg DM the ING group was higher than ORG. The liver GSH-Px activity was higher in the ORG group vs. ING at concentration 0.9 and 2.7 mg supplemental Se/kg DM. The GSH/GSSG ratio was the highest in animals fed 0.3 mg supplemental Se/kg DM of ORG. Selenium liver concentration increased linearly with the supplemental Se concentration in the diet (y = 0.0583 + 0.4254x, R2 = 0.92, P < 0.0001), regardless of source. Total meat cholesterol was greater (P < 0.001) in CON (control) vs. SUP (supplemented, regardless source) group. The muscle GSH-Px activity was higher (P < 0.001) in SUP vs. CON and increased (P < 0.004) with increasing supplemental Se concentrations. There was an increase on very low-density lipoprotein (VLDL), glucose, and triglycerides in ORG vs. ING (P ≤ 0.035). In general, serum Se was higher (P < 0.001) in SUP vs. CON and increased with increasing supplemental Se concentration. Lastly, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) concentration was lower (P = 0.002) in SUP (0.39 ng/mL) vs. CON (0.55 ng/mL). Selenium supplementation with different sources and concentrations has the potential to affect cholesterol metabolism by affecting GSH/GSSG ratio, GSH-Px, and the HMGCR.

Green tea infusion prevents diabetic nephropathy aggravation in recent-onset type 1 diabetes regardless of glycemic control.

ETHNOPHARMACOLOGICAL RELEVANCE: Green tea, traditionally used as antidiabetic medicine, positively affects the diabetic nephropathy. It was assumed that these beneficial effects were due to the hypoglycemiant capacity of the tea, wich reduces the glycemic overload and, consequently, the advanced glycation end products rate and oxidative damage. However, these results are still controversial, since tea is not always able to exert a hypoglycemic action, as demonstrated by previous studies. AIM: Investigate if green tea infusion can generate positive outcomes for the kidney independently of glycemic control, using a model of severe type 1 diabetes. MATERIAL AND METHODS: We treated streptozotocin type 1 diabetic young rats with 100 mg/kg of green tea, daily, for 42 days, and evaluated the serum and tissue markers for stress and function. We also analyzed the ion dynamics in the organ and the morphological alterations promoted by diabetes and green tea treatment. Besides, we analyzed, by an in silico approach, the interactions of the green tea main catechins with the proteins expressed in the kidney. RESULTS: Our findings reveal that the components of green tea can interact with the proteins participating in cell signaling pathways that regulate energy metabolism, including glucose and glycogen synthesis, glucose reabsorption, hypoxia management, and cell death by apoptosis. Such interaction reduces glycogen accumulation in the organ, and protects the DNA. These results also reflect in a preserved glomerulus morphology, with improvement in pathological features, and suggesting a prevention of kidney function impairment. CONCLUSION: Our results show that such benefits are achieved regardless of the blood glucose status, and are not dependent on the reduction of hyperglycemia.

Free Radical Scavengers Prevent Argininosuccinic Acid-Induced Oxidative Stress in the Brain of Developing Rats: a New Adjuvant Therapy for Argininosuccinate Lyase Deficiency?

Tissue accumulation and high urinary excretion of argininosuccinate (ASA) is the biochemical hallmark of argininosuccinate lyase deficiency (ASLD), a urea cycle disorder mainly characterized by neurologic abnormalities, whose pathogenesis is still unknown. Thus, in the present work, we evaluated the in vitro and in vivo effects of ASA on a large spectrum of oxidative stress parameters in brain of adolescent rats in order to test whether disruption of redox homeostasis could be involved in neurodegeneration of this disorder. ASA provoked in vitro lipid and protein oxidation, decreased reduced glutathione (GSH) concentrations, and increased reactive oxygen species generation in cerebral cortex and striatum. Furthermore, these effects were totally prevented or attenuated by the antioxidants melatonin and GSH. Similar results were obtained by intrastriatal administration of ASA, in addition to increased reactive nitrogen species generation and decreased activities of superoxide dismutase, glutathione peroxidase, and glutathione S-transferase. It was also observed that melatonin and N-acetylcysteine prevented most of ASA-induced in vivo pro-oxidant effects in striatum. Taken together, these data indicate that disturbance of redox homeostasis induced at least in part by high brain ASA concentrations per se may potentially represent an important pathomechanism of neurodegeneration in patients with ASLD and that therapeutic trials with appropriate antioxidants may be an adjuvant treatment for these patients.

Cafestol, a diterpene molecule found in coffee, induces leukemia cell death.

To evaluate the antitumor properties of Cafestol four leukemia cell lines were used (NB4, K562, HL60 and KG1). Cafestol exhibited the highest cytotoxicity against HL60 and KG1 cells, as evidenced by the accumulation of cells in the sub-G1 fraction, mitochondrial membrane potential reduction, accumulation of cleaved caspase-3 and phosphatidylserine externalization. An increase in CD11b and CD15 differentiation markers with attenuated ROS generation was also observed in Cafestol-treated HL60 cells. These results were similar to those obtained following exposure of the same cell line to cytarabine (Ara-C), an antileukemic drug. Cafestol and Ara-C reduced the clonogenic potential of HL60 cells by 100%, but Cafestol spared murine colony forming unit- granulocyte/macrophage (CFU-GM), which retained their clonogenicity. The co-treatment of Cafestol and Ara-C reduced HL60 cell viability compared with both drugs administered alone. In conclusion, despite the distinct molecular mechanisms involved in the activity of Cafestol and Ara-C, a similar cytotoxicity towards leukemia cells was observed, which suggests a need for prophylactic-therapeutic pre-clinical studies regarding the anticancer properties of Cafestol.