Caffeine improves the cytotoxic effect of dacarbazine on B16F10 murine melanoma cells.

OBJECTIVE: Caffeine has been studied as a potentiating agent in chemotherapy against some types of cancer, but there are few reports on its effects on melanoma. This study aimed to investigate caffeine's ability to enhance the effects of dacarbazine in vitro. MATERIALS AND METHODS: Murine melanoma B16F10 cells were treated 24 h with 1-40 µM caffeine. We evaluated cytotoxicity, DNA damage, apoptosis, and oxidative lesion induced by dacarbazine associated with caffeine. The metabolization of these drugs, as well as immunocytochemical labeling, were also evaluated. CONCLUSIONS: The pre-treatment with caffeine showed to be more effective. Caffeine potentiated dacarbazine-induced cytotoxic effects by increasing dacarbazine biotransformation, apoptosis, DNA damage, and malondialdehyde levels; also, caffeine reduced Ki67 and ERK1/2 nuclear labeling and increased p53 labeling in B16F10 cells. In our experiment, caffeine promoted modifications associated with dacarbazine metabolism by viable cells potentiating this antineoplastic drug. These promising results should be further evaluated in experimental models in vivo.

Consequences of nano and microplastic exposure in rodent models: the known and unknown.

The ubiquitous nature of micro- (MP) and nanoplastics (NP) is a growing environmental concern. However, their potential impact on human health remains unknown. Research increasingly focused on using rodent models to understand the effects of exposure to individual plastic polymers. In vivo data showed critical exposure effects depending on particle size, polymer, shape, charge, concentration, and exposure routes. Those effects included local inflammation, oxidative stress, and metabolic disruption, leading to gastrointestinal toxicity, hepatotoxicity, reproduction disorders, and neurotoxic effects. This review distillates the current knowledge regarding rodent models exposed to MP and NP with different experimental designs assessing biodistribution, bioaccumulation, and biological responses. Rodents exposed to MP and NP showed particle accumulation in several tissues. Critical responses included local inflammation and oxidative stress, leading to microbiota dysbiosis, metabolic, hepatic, and reproductive disorders, and diseases exacerbation. Most studies used MP and NP commercially provided and doses higher than found in environmental exposure. Hence, standardized sampling techniques and improved characterization of environmental MP and NP are needed and may help in toxicity assessments of relevant particle mixtures, filling knowledge gaps in the literature.

Oxidative Stress in Caffeine Action on the Proliferation and Death of Human Breast Cancer Cells MCF-7 and MDA-MB-231.

To investigate the effects of caffeine on the proliferation and death of human breast cancer cells MCF-7 and MDA-MB-231. Cells were exposed to 1, 2.5, 5 and 10 mM of caffeine during 24 h, and oxidative stress (OS), cell proliferation and death, metabolic activity and DNA lesions were evaluated in the collected samples. Caffeine was cytotoxic to the cell lines analyzed, reducing cell proliferation and viability by interfering with the cellular metabolism and with lysosomal function. Although the cells presented different behaviors to treatment, in both cell lines, the drug induced OS and predominantly apoptosis. MCF-7 cells responded to OS induction (lipid peroxidation) increasing their antioxidant defenses. However, the OS generated induced oxidative DNA lesions, a finding not observed in MDA-MB-231 cells. The association of different scavengers with caffeine did not result in the recovery of cell viability, which suggests that it is not possible to attribute the caffeine induction of OS to only one of the specific ROS analyzed (superoxide anion, singlet oxygen and peroxyl radical). These results are promising and suggest that caffeine may be a good target for studies to prove its usefulness as an adjuvant in breast cancer treatment.

COVID-19: The question of genetic diversity and therapeutic intervention approaches.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.

Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats.

BACKGROUND/AIMS: Trichilia catigua A. Juss., known as "catuaba" in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF) of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. METHODS: Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group). The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ) injection (35 mg/kg). Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. RESULTS: EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the number of pancreatic ß-cells and the size of the islets had increased by ß-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. CONCLUSION: The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats.

Protective effect of metformin in an aberrant crypt foci model induced by 1,2-dimethylhydrazine: Modulation of oxidative stress and inflammatory process.

Colorectal Cancer (CRC) is the third most frequent type of cancer worldwide. In the past few years, studies have revealed a protective effect of metformin (MET-an anti-hyperglycemic drug, used to treat type 2 diabetes), against CRC. The protective effect of MET has been associated with AMPK activation (and mTOR inhibition), resulting in suppressed protein synthesis, and reduced cell proliferation in malignant transformed cells. To elucidate new mechanisms for the protective effect of metformin, we evaluated the oxidative stress and inflammatory process modulation, since these processes are strictly involved in colorectal carcinogenesis. The present study evaluated the protective effect of MET in a CRC model induced by 1,2-dimethylhydrazine (DMH) in Balb/c female mice. The simultaneous/continuous treatment (administration of MET and DMH simultaneously), revealed protective activity of MET, preventing the formation of aberrant crypt foci (ACF) in 71.4% at distal colon sections, and was able to restore basal labeling of apoptosis. Treatment with MET also reduced the inflammatory process induced by DMH, resulting in of the reduction of oxidative stress and nitric oxide related parameters. © 2016 Wiley Periodicals, Inc.

Cytotoxicity of citral against melanoma cells: The involvement of oxidative stress generation and cell growth protein reduction.

Citral is a natural compound that has shown cytotoxic and antiproliferative effects on breast and hematopoietic cancer cells; however, there are few studies on melanoma cells. Oxidative stress is known to be involved in all stages of melanoma development and is able to modulate intracellular pathways related to cellular proliferation and death. In this study, we hypothesize that citral exerts its cytotoxic effect on melanoma cells by the modulation of cellular oxidative status and/or intracellular signaling. To test this hypothesis, we investigated the antiproliferative and cytotoxic effects of citral on B16F10 murine melanoma cells evaluating its effects on cellular oxidative stress, DNA damage, cell death, and important signaling pathways, as these pathways, namely, extracellular signal-regulated kinases 1/2 (ERK1/2), AKT, and phosphatidylinositol-3 kinase, are involved in cell proliferation and differentiation. The p53 and nuclear factor kappa B were also investigated due to their ability to respond to intracellular stress. We observed that citral exerted antiproliferative and cytotoxic effects in B16F10; induced oxidative stress, DNA lesions, and p53 nuclear translocation; and reduced nitric oxide levels and nuclear factor kappa B, ERK1/2, and AKT. To investigate citral specificity, we used non-neoplastic human and murine cells, HaCaT (human skin keratinocytes) and NIH-3T3 cells (murine fibroblasts), and observed that although citral effects were not specific for cancer cells, non-neoplastic cells were more resistant to citral than B16F10. These findings highlight the potential clinical utility of citral in melanoma, with a mechanism of action involving the oxidative stress generation, nitric oxide depletion, and interference in signaling pathways related to cell proliferation.

Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor ß1 induction.

The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 µM) and experimental concentrations of metformin (1000 and 5000 µM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor ß1 (TGF-ß1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-ß1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer.

Reactive oxygen species play a role in muscle wasting during thyrotoxicosis.

The role of reactive oxygen species (ROS) in muscle protein hydrolysis and protein oxidation in thyrotoxicosis has not been explored. This study indicates that ROS play a role in skeletal muscle wasting pathways in thyrotoxicosis. Two experimental groups (rats) were treated for 5 days with either 3,3',5-triiodothyronine (HT) or HT with α-tocopherol (HT + αT). Two controls were used, vehicle (Control) and control treated with αT (Control + αT). Serum T3, peritoneal fat, serum glycerol, muscle and body weight, temperature, mitochondrial metabolism (cytochrome c oxidase activity), oxidative stress parameters and proteolytic activities were examined. High body temperature induced by HT returned to normal when animals were treated with αT, although total body and muscle weight did not. An increase in lipolysis was observed in the HT + αT group, as peritoneal fat decreased significantly together with an increase in serum glycerol. GSH, GSSG and total radical-trapping antioxidant parameter (TRAP) decreased and catalase activity increased in the HT group. The glutathione redox ratio was higher in HT + αT than in both HT and Control + αT groups. Carbonyl proteins, AOPP, mitochondrial and chymotrypsin-like proteolytic activities were higher in the HT group than in the Control. HT treatment with αT restored mitochondrial metabolism, TRAP, carbonyl protein, chymotrypsin-like activity and AOPP to the level as that of the Control + αT. Calpain activity was lower in the HT + αT group than in HT and Control + αT and superoxide dismutase (SOD) activity was higher in the HT + αT group than in the Control + αT. Although αT did not reverse muscle loss, ROS was involved in proteolysis to some degree.

Sonicated polyethylene terephthalate nano- and micro-plastic-induced inflammation, oxidative stress, and autophagy in vitro.

The environmental presence of nano- and micro-plastic particles (NMPs) is suspected to have a negative impact on human health. Environmental NMPs are difficult to sample and use in life science research, while commercially available plastic particles are too morphologically uniform. Additionally, this NMPs exposure exhibited biological effects, including cell internalization, oxidative stress, inflammation, cellular adaptation, and genotoxicity. Therefore, developing new methods for producing heterogenous NMPs as observed in the environment is important as reference materials for research. Thus, we aimed to generate and characterize NMPs suspensions using a modified ultrasonic protocol and to investigate their biological effects after exposure to different human cell lines. To this end, we produced polyethylene terephthalate (PET) NMPs suspensions and characterized the particles by dynamic light scattering and scanning electron microscopy. Ultrasound treatment induced polymer degradation into smaller and heterogeneous PET NMPs shape fragments with similar surface chemistry before and after treatment. A polydisperse suspension of PET NMPs with 781 nm in average size and negative surface charge was generated. Then, the PET NMPs were cultured with two human cell lines, A549 (lung) and HaCaT (skin), addressing inhalation and topical exposure routes. Both cell lines interacted with and have taken up PET NMPs as quantified via cellular granularity assay. A549 but not HaCaT cell metabolism, viability, and cell death were affected by PET NMPs. In HaCaT keratinocytes, large PET NMPs provoked genotoxic effects. In both cell lines, PET NMPs exposure affected oxidative stress, cytokine release, and cell morphology, independently of concentration, which we could relate mechanistically to Nrf2 and autophagy activation. Collectively, we present a new PET NMP generation model suitable for studying the environmental and biological consequences of exposure to this polymer.

Oxidative status and chymotrypsin-like activity in right and left ventricle hypertrophy in an experimental model of emphysema.

Although cardiac muscle hypertrophy has been studied in association with several diseases, its mechanism in patients with emphysema, in particular in relation to oxidative stress and proteolysis, remains unknown. The role of oxidative stress and proteolysis in right and left ventricle hypertrophy was investigated in hamsters with emphysema induced by 2 different doses of papain (20mg/mL, E20 and 40mg/mL, E40). The thickness of the ventricles, total and cardiac weight, lipid peroxidation, carbonyl proteins, total antioxidant capacity (TAC), and proteasomal proteolytic activity were evaluated in the right ventricle (RV) and the left ventricle (LV) of control and emphysema hamsters. RV thickness was increased by 12% in the E20 group and by 29% in the E40 group. Lipid peroxidation measured by chemiluminescence was increased in the E40 group (from 3350.68±392.44URL/g tissue to 4696.63±1076.70URL/g tissue, p<0.05). TAC also increased only in the E40 group. In the LV, chemiluminescence values increased from 4044.77±503.39 to 5517.10±388.27 in the E20 group and to 8169.14±1748.77URL/g tissue in the E40 group (p<0.05, both). TAC significantly increased in the E20 and E40 groups. No differences were detected in substances reactive to thiobarbituric acid or carbonyl proteins when comparing ventricles or doses. Chymotrypsin-like proteolytic activity significantly decreased in both groups and ventricles. Emphysema can induce right and left ventricle lipid peroxidation and result in antioxidant mobilization. These data together support the idea that cardiac hypertrophy in response to emphysema is mediated in part by proteolytic pathways with involvement of reactive species.

Lung injury-dependent oxidative status and chymotrypsin-like activity of skeletal muscles in hamsters with experimental emphysema.

BACKGROUND: Peripheral skeletal muscle is altered in patients suffering from emphysema and chronic obstructive pulmonary disease (COPD). Oxidative stress have been demonstrated to participate on skeletal muscle loss of several states, including disuse atrophy, mechanical ventilation, and chronic diseases. No evidences have demonstrated the occurance in a severity manner. METHODS: We evaluated body weight, muscle loss, oxidative stress, and chymotrypsin-like proteolytic activity in the gastrocnemius muscle of emphysemic hamsters. The experimental animals had 2 different severities of lung damage from experimental emphysema induced by 20 mg/mL (E20) and 40 mg/mL (E40) papain. RESULTS: The severity of emphysema increased significantly in E20 (60.52 ± 2.8, p < 0.05) and E40 (52.27 ± 4.7; crossed the alveolar intercepts) groups. As compared to the control group, there was a reduction on body (171.6 ± 15.9 g) and muscle weight (251.87 ± 24.87 mg) in the E20 group (157.5 ± 10.3 mg and 230.12 ± 23.52 mg, for body and muscle weight, respectively), which was accentuated in the E40 group (137.4 ± 7.2 g and 197.87 ± 10.49 mg, for body and muscle weight, respectively). Additionally, the thiobarbituric acid reactive substances (TBARS), tert-butyl hydroperoxide-initiated chemiluminescence (CL), carbonylated proteins, and chymotrypsin-like proteolytic activity were elevated in the E40 group as compared to the E20 group (p < 0.05 for all comparisons). The severity of emphysema significantly correlated with the progressive increase in CL (r = -0.95), TBARS (r = -0.98), carbonyl proteins (r = -0.99), and chymotrypsin-like proteolytic activity (r = -0.90). Furthermore, augmentation of proteolytic activity correlated significantly with CL (r = 0.97), TBARS (r = 0.96), and carbonyl proteins (r = 0.91). CONCLUSIONS: Taken together, the results of the present study suggest that muscle atrophy observed in this model of emphysema is mediated by increased muscle chymotrypsin-like activity, with possible involvement of oxidative stress in a severity-dependent manner.

Medical Gas Plasma Technology Combines with Antimelanoma Therapies and Promotes Immune-Checkpoint Therapy Responses.

Strategies to improve activity and selectivity are major goals in oncological drug development. Medical gas plasma therapy has been subject to intense research in dermatooncology recently. Based on partial gas ionization, this approach is exceptional in generating a variety of reactive oxygen species simultaneously that can be applied locally at the tumor side. It is hypothesized that combined gas plasma treatment can potentiate drug responses in the treatment of melanoma. Using a plasma jet approved as medical device in Europe, a systematic screening of 46 mitochondria-targeted drugs identifies five agents synergizing in vitro and in vivo. Increased intratumoral leucocyte infiltration points to immunomodulatory aspects of the treatment, motivating to investigate responses to immune checkpoint blockade in combination with plasma. Tumor growth is monitored based on bioluminescent imaging, and single-cell suspensions are retrieved from each tumor to characterize tumor-infiltrating leucocytes using multicolor flow cytometry. Gene expression profiling is done using a validated NanoString panel targeting 770 genes specifically designed for immuno-oncological research. Cell type abundancies are characterized from bulk RNA samples using the CIBERSORT computational framework. Collectively, the results indicate that local application of medical gas plasma technology synergizes with mitochondria-targeted drugs and anti-PD1 checkpoint therapy in treating melanoma.

Conductive Gas Plasma Treatment Augments Tumor Toxicity of Ringer's Lactate Solutions in a Model of Peritoneal Carcinomatosis.

Reactive species generated by medical gas plasma technology can be enriched in liquids for use in oncology targeting disseminated malignancies, such as metastatic colorectal cancer. Notwithstanding, reactive species quantities depend on the treatment mode, and we recently showed gas plasma exposure in conductive modes to be superior for cancer tissue treatment. However, evidence is lacking that such a conductive mode also equips gas plasma-treated liquids to confer augmented intraperitoneal anticancer activity. To this end, employing atmospheric pressure argon plasma jet kINPen-treated Ringer's lactate (oxRilac) in a CT26-model of colorectal peritoneal carcinomatosis, we tested repeated intraabdominal injection of such remotely or conductively oxidized liquid for antitumor control and immunomodulation. Enhanced reactive species formation in conductive mode correlated with reduced tumor burden in vivo, emphasizing the advantage of conduction over the free mode for plasma-conditioned liquids. Interestingly, the infiltration of lymphocytes into the tumors was equally enhanced by both treatments. However, significantly lower levels of interleukin (IL)4 and IL13 and increased levels of IL2 argue for a shift in intratumoral T-helper cell subpopulations correlating with disease control. In conclusion, our data argue for using conductively over remotely prepared plasma-treated liquids for anticancer treatment.

Decreased plasma H2O2 levels are associated with the pathogenesis leading to COVID-19 worsening and mortality.

Oxidative Stress (OS) is involved in the pathogenesis of COVID-19 and in the mechanisms by which SARS-CoV-2 causes injuries to tissues, leading to cytopathic hypoxia and ultimately multiple organ failure. The measurement of blood glutathione (GSH), H2O2, and catalase activity may help clarify the pathophysiology pathways of this disease. We developed and standardized a sensitive and specific chemiluminescence technique for H2O2 and GSH measurement in plasma and red blood cells of COVID-19 patients admitted to the intensive care unit (ICU). Contrary to what was expected, the plasma concentration of H2O2 was substantially reduced (10-fold) in COVID-19 patients compared to the healthy control group. From the cohort of patients discharged from the hospital and those who were deceased, the former showed a 3.6-fold and the later 16-fold H2O2 reduction compared to the healthy control. There was a 4.4 reduction of H2O2 concentration in the deceased group compared to the discharged group. Interestingly, there was no variation in GSH levels between groups, and reduced catalase activity was found in discharged and deceased patients compared to control. These data represent strong evidence that H2O2 is converted into highly reactive oxygen species (ROS), leading to the worst prognosis and death outcome in COVID-19 patients admitted to ICU. Considering the difference in the levels of H2O2 between the control group and the deceased patients, it is proposed the quantification of plasma H2O2 as a marker of disease progression and the induction of the synthesis of antioxidant enzymes as a strategy to reduce the production of oxidative stress during severe COVID-19.HighlightsH2O2 plasma levels is dramatically reduced in patients who deceased compared to those discharged and to the control group.Plasmatic quantification of H2O2 can be possibly used as a predictor of disease progression.Catalase activity is reduced in COVID-19.GSH levels remain unchanged in COVID-19 compared to the control group.

Role of papillary thyroid carcinoma patients with Hashimoto thyroiditis: evaluation of oxidative stress and inflammatory markers.

PURPOSE: Papillary thyroid carcinoma (PTC) is the most frequent subtype of thyroid cancer; Hashimoto's thyroiditis (HT), autoimmune disease, commonly affects the thyroid gland; there is possibly a correlation between both, but the exact mechanisms that involve this relationship are still under debate. Since oxidative stress (OS) and the inflammatory environment participate in the development of several types of cancer, the objective of the present study was to establish the microenvironment and systemic participation of OS and inflammatory markers in patients with PTC and HT. METHODS: Blood and tissue samples were collected from 115 patients: BENIGN (n = 63); PTC (n = 27); HT (n = 15) and PTC + HT (n = 10), and sixty-three were samples from healthy individuals (control group). RESULTS: Superoxide dismutase, Catalase, reduced Glutathione, markers of lipid peroxidation and inflammation were evaluated in blood. Immunohistochemistry was performed on 3-nitrotyrosine, 4-hydroxynonenal, Ki-67 and VEGF. The results indicate that antioxidant enzymes were more active in groups with thyroid disorders compared to control, while the concentration of Reduced glutathione was reduced in BENIGN and PTC groups. When PTC and PTC + HT groups were analyzed, no significant differences were found in relation to the antioxidant defense and inflammatory markers. The ability to contain the induced lipid peroxidation was lower and a high level of malondialdehyde was observed in the PTC group. All immunohistochemical markers had higher scores in the PTC group compared to PTC + HT. CONCLUSION: There was a more pronounced presence of OS and a greater activity of cell proliferation and angiogenesis markers in PTC than in PTC + HT group.

The Anticancer Efficacy of Plasma-Oxidized Saline (POS) in the Ehrlich Ascites Carcinoma Model In Vitro and In Vivo.

Cold physical plasma, a partially ionized gas rich in reactive oxygen species (ROS), is receiving increasing interest as a novel anticancer agent via two modes. The first involves its application to cells and tissues directly, while the second uses physical plasma-derived ROS to oxidize liquids. Saline is a clinically accepted liquid, and here we explored the suitability of plasma-oxidized saline (POS) as anticancer agent technology in vitro and in vivo using the Ehrlich Ascites Carcinoma (EAC) model. EAC mainly grows as a suspension in the peritoneal cavity of mice, making this model ideally suited to test POS as a putative agent against peritoneal carcinomatosis frequently observed with colon, pancreas, and ovarium metastasis. Five POS injections led to a reduction of the tumor burden in vivo as well as in a decline of EAC cell growth and an arrest in metabolic activity ex vivo. The treatment was accompanied by a decreased antioxidant capacity of Ehrlich tumor cells and increased lipid oxidation in the ascites supernatants, while no other side effects were observed. Oxaliplatin and hydrogen peroxide were used as controls and mediated better and worse outcomes, respectively, with the former but not the latter inducing profound changes in the inflammatory milieu among 13 different cytokines investigated in ascites fluid. Modulation of inflammation in the POS group was modest but significant. These results promote POS as a promising candidate for targeting peritoneal carcinomatosis and malignant ascites and suggest EAC to be a suitable and convenient model for analyzing innovative POS approaches and combination therapies.

Extended light period in the maternal circadian cycle impairs the reproductive system of the rat male offspring.

Alterations in the circadian cycle are known to cause physiological disorders in the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes in adult individuals. Therefore, the present study aimed to evaluate whether exposure of pregnant rats to constant light can alter the reproductive system development of male offspring. The dams were divided into two groups: a light-dark group (LD), in which pregnant rats were exposed to an LD photoperiod (12 h/12 h) and a light-light (LL) group, in which pregnant rats were exposed to a photoperiod of constant light during the gestation period. After birth, offspring from both groups remained in the normal LD photoperiod (12 h/12 h) until adulthood. One male of each litter was selected and, at adulthood (postnatal day (PND) 90), the trunk blood was collected to measure plasma testosterone levels, testes and epididymis for sperm count, oxidative stress and histopathological analyses, and the spermatozoa from the vas deferens to perform the morphological and motility analyses. Results showed that a photoperiod of constant light caused a decrease in testosterone levels, epididymal weight and sperm count in the epididymis, seminiferous tubule diameter, Sertoli cell number, and normal spermatozoa number. Histopathological damage was also observed in the testes, and stereological alterations, in the LL group. In conclusion, exposure to constant light during the gestational period impairs the reproductive system of male offspring in adulthood.

SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression.

Since the WHO declared COVID-19 a pandemic, a great effort has been made to understand this serious disease. Thousands of studies are being devoted to understanding its epidemiology, its molecular characteristics, its mechanisms, and the clinical evolution of this viral infection. However, little has been published on its pathogenesis and the host response mechanisms in the progress of the disease. Therefore, we propose a hypothesis based on strong scientific documentation, associating oxidative stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia. Finally, we suggest a therapeutic strategy to reduce oxidative stress using antioxidants, NF-κB inhibitors, Nrf2 activators, and iron complexing agents. We believe that this hypothesis can guide new studies and therapeutic strategies on this topic.

Thyroid cancer and thyroid autoimmune disease: A review of molecular aspects and clinical outcomes.

Thyroid cancer (TC) is the most prevalent malignant neoplasm that affects the endocrine system. Hashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is the most common autoimmune thyroid disease (AITD) that, together with Graves' disease (GD), represent the main autoimmune diseases that affect the thyroid gland. Some studies suggest a greater risk of AITD and the development of TC, while others, investigate its relationship with TC progression and patient prognosis. In this review, we have analyzed published data on the molecular aspects related to the association between AITD and TC, addressing their influence on TC progression, diagnosis, and prognosis of the patients. MEDLINE database (PubMed) platform was used as a search engine and the original articles related to the topic were selected using the keywords combination "thyroid cancer and Hashimoto thyroiditis" or "thyroid carcinoma and thyroid autoimmune disease". After the selection, we categorized the main findings of the papers into four topics: antitumor immunity, tumor progression, diagnosis, and prognosis. Although most of the studies have pointed out the presence of AITD as a factor that increases the risk of TC, few molecular mechanisms to support this conclusion have been described. Additionally, little information is available to explain, pathophysiologically, the effects of autoimmunity in TC diagnosis, progression, and prognosis.