Combined Use of Intranasal Methylprednisolone and Allopregnanolone: Revisiting Anti-inflammatory and Remyelinating Treatment in a Murine Model of Multiple Sclerosis.

Background: Multiple sclerosis (MS) is a demyelinating, neuroinflammatory, progressive disease that severely affects human health of young adults. Neuroinflammation (NI) and demyelination, as well as their interactions, are key therapeutic targets to halt or slow disease progression. Potent steroidal anti-inflammatory drugs such as methylprednisolone (MP) and remyelinating neurosteroids such as allopregnanolone (ALLO) could be co-administered intranasally to enhance their efficacy by providing direct access to the central nervous system (CNS).

Exploring the Mechanisms Underlying Cellular Uptake and Activation of Dendritic Cells by the GK-1 Peptide.

The use of peptides for cancer immunotherapy is a promising and emerging approach that is being intensively explored worldwide. One such peptide, GK-1, has been shown to delay the growth of triple-negative breast tumors in mice, reduce their metastatic capacity, and reverse the intratumor immunosuppression that characterizes this model. Herein, it is demonstrated that GK-1 is taken up by bone marrow dendritic cells in a dose-dependent manner 15 min after exposure, more efficiently at 37 °C than at 4 °C, implying an entrance into the cells by energy-independent and -dependent processes through clathrin-mediated endocytosis.

COVID-19 in Brazilian Pediatric Patients: A Retrospective Cross-Sectional Study with a Predictive Model for Hospitalization.

Background: This study was conducted to ascertain the most frequent symptoms of COVID-19 infection at first consultation in a pediatric cohort and to devise a predictive model for hospitalization.

Methods: This is a retrospective cross-sectional study of 1028 Brazilian patients aged <18 years with SARS-CoV-2 infection in a single reference hospital in the first year of the pandemic. Clinical, demographic, laboratory, and disease spectrum data were analyzed via multivariate logistic regression modeling to develop a predictive model of factors linked to hospitalization.

Anti-adipogenic effect of Malva parviflora on 3T3-L1 adipocytes.

Malva parviflora has shown anti-inflammatory, antihypertensive, antihyperlipidemic, and hypoglycemic effects. This study is aimed to evaluate the anti-adipogenic effect of M. parviflora on 3T3-L1 adipocytes.

Putrescine Supplementation Limits the Expansion of pks+ Escherichia coli and Tumor Development in the Colon.

Unlabelled: Escherichia coli that harbor the polyketide synthase (pks) genomic island produce colibactin and are associated with sporadic colorectal cancer development. Given the considerable prevalence of pks+ bacteria in healthy individuals, we sought to identify strategies to limit the growth and expansion of pks+ E. coli.

Increased levels of regulatory T cells and IL-10-producing regulatory B cells are linked to improved clinical outcome in Parkinson's disease: a 1-year observational study.

Whilst the contribution of peripheral and central inflammation to neurodegeneration in Parkinson's disease and the role of the immune response in this disorder are well known, the effects of the anti-inflammatory response on the disease have not been described in depth. This study is aimed to assess the changes in the regulatory/inflammatory immune response in recently diagnosed, untreated PD patients and a year after. Twenty-one PD patients and 19 healthy controls were included and followed-up for 1 year.

Multi-vehicle adaptive 3D mapping for targeted ocean sampling.

Expanding spatial presentation from two-dimensional profile transects to three-dimensional ocean mapping is key for a better understanding of ocean processes. Phytoplankton distributions can be highly patchy and the accurate identification of these patches with the context, variability, and uncertainty of measurements on relevant scales is difficult to achieve. Traditional sampling methods, such as plankton nets, water samplers and in-situ vertical sensors, provide a snapshot and often miss the fine-scale horizontal and temporal variability.

Role of Angiotensin II in Non-Alcoholic Steatosis Development.

Fatty liver is a multifactorial disease characterized by excessive accumulation of lipids in hepatocytes (steatosis), insulin resistance, oxidative stress, and inflammation. This disease has a major public health impact because it is the first stage of a chronic and degenerative process in the liver that can lead to steatohepatitis, cirrhosis, and liver cancer. Although this disease is mainly diagnosed in patients with obesity, type 2 diabetes mellitus, and dyslipidemia, recent evidence indicates that vasoactive hormones such as angiotensin II (ANGII) not only promote endothelial dysfunction (ED) and hypertension, but also cause fatty liver, increase adipose tissue, and develop a pro-steatotic environment characterized by a low-grade systemic pro-inflammatory and pro-oxidant state, with elevated blood lipid levels.

Hydroalcoholic extract from (Jacq.) S.w. root reverses oleic acid-induced steatosis and insulin resistance .

Steatosis is characterized by fat accumulation and insulin resistance (IR) in hepatocytes, which triggers a pro-oxidant, pro-inflammatory environment that may eventually lead to cirrhosis or liver carcinoma. This work was aimed to assess the effect of root hydroalcoholic extract (rSe-HA) (rich in cinnamic and coumaric acid, among other phenolic compounds) on triglyceride esterification, lipid degradation, AMPK expression, and the phosphorylation of insulin receptor in a Ser residue, as well as on the redox status, malondialdehyde (MDA) production, and the production of proinflammatory cytokines in an model of steatosis induced by oleic acid, to help develop a phytomedicine that could reverse this pathology. rSe-HA reduced triglyceride levels in hepatocyte lysates, increased lipolysis by activating AMPK at Thr, and improved the redox status, as evidenced by the concentration of glycerol and formazan, respectively.

Intranasal Versus Intravenous Dexamethasone to Treat Hospitalized COVID-19 Patients: A Randomized Multicenter Clinical Trial.

Background: SARS-CoV2 induces flu-like symptoms that can rapidly progress to severe acute lung injury and even death. The virus also invades the central nervous system (CNS), causing neuroinflammation and death from central failure. Intravenous (IV) or oral dexamethasone (DXM) reduced 28 d mortality in patients who required supplemental oxygen compared to those who received conventional care alone.

Caveats of chimpanzee ChAdOx1 adenovirus-vectored vaccines to boost anti-SARS-CoV-2 protective immunity in mice.

Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy.

Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery.

Purpose: Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells.

Aqueous Fraction from Aerial Parts Attenuates Angiotensin II-Induced Endothelial Dysfunction In Vivo by Activating Akt.

Background: Endothelial dysfunction (ED) is a marker of vascular damage and a precursor of cardiovascular diseases such as hypertension, which involve inflammation and organ damage. Nitric oxide (NO), produced by eNOS, which is induced by pAKT, plays a crucial role in the function of a healthy endothelium.

Methods: A combination of subfractions SF1 and SF3 (C4) of the aqueous fraction from (Cs-Aq) was evaluated to control endothelial dysfunction in vivo and on HMEC-1 cells to assess the involvement of pAkt in vitro.

Prospective Study to Analyze the Concordance Between a Standardized Visual Method With Pathology to stratify Nonalcoholic Fatty Liver Disease in Cadaveric Liver Grafts Evaluated for Transplantation.

Background: The main challenge of liver transplantation is the discrepancy in demand and availability. Marginal grafts or full organs from donors with expansion criteria have been considered to reduce the shortage and assist a greater number of patients. Nonalcoholic fatty liver disease (NAFLD) is one of the most important defining criteria for expanded criteria organs.

Photophysiologically active green, red, and brown macroalgae living in the Arctic Polar Night.

Arctic macroalgae species have developed different growth strategies to survive extreme seasonal changes in irradiance in polar regions. We compared photophysiological parameters such as the light saturation parameter (E) and pigment composition of green, red, and brown macroalgae collected in January (Polar Night) and October 2020 (end of the light season). Macroalgae in January appeared healthier (morphologically) and had longer lamina (new growth) than those in October.

Can sPD-1 and sPD-L1 Plasma Concentrations Predict Treatment Response among Patients with Extraparenchymal Neurocysticercosis?

Extraparenchymal neurocysticercosis (EP-NC) is a chronic, potentially life-threatening disease that responds poorly to initial anthelmintic drug therapy. A depressed specific reactivity of peripheral lymphocytes and an increased level of specific Tregs accompanies EP-NC. The immune checkpoint pathway PD-1 and its ligand PD-L1 downregulates effector T cells, causing specific immune suppression in chronic diseases.

GK-1 effectively reduces angiogenesis and prevents T cell exhaustion in a breast cancer murine experimental model.

Breast cancer is the leading malignancy in women worldwide, both in terms of incidence and mortality. Triple-negative breast cancer (TNBC) is the type with the worst clinical outcomes and with fewer therapeutic options than other types of breast cancer. GK-1 is a peptide that in the experimental model of the metastatic 4T1 breast cancer has demonstrated anti-tumor and anti-metastatic properties.

Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection.

Background: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC.

and Cysticidal Effects of Cell Suspensions.

Parasitic diseases are a major public health problem worldwide. Plant-derived products appear to be ideal candidates from a biotechnological perspective, being sustainable and environmentally friendly. The antiparasitic properties of have been attributed to some of its components, including papain and other compounds that are concentrated in the latex and seeds.

Low responsiveness of peripheral lymphocytes in extraparenchymal neurocysticercosis.

Background: The morbidity and mortality of extraparenchymal neurocysticercosis (EP-NC) remain high and effectiveness of current medical treatment is suboptimal. Various factors have been implicated in the severity of EP-NC and in the poor response to treatment, but the possible role of host immune and endocrine systems has not yet been examined thoroughly.

Methodology/principal Findings: 42 participants with EP-NC before receiving standard treatment and 25 healthy controls were included in the study.

α-Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple-negative breast cancer model.

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor; therefore, TNBC lacks targeted therapy, and chemotherapy is the only available treatment for this illness but causes side effects. A putative strategy for the treatment of TNBC could be the use of the polyphenols such as α-Mangostin (α-M), which has shown anticancerogenic effects in different cancer models and can modulate the inflammatory and prooxidant state in several pathological models. The redox state, oxidative stress (OS), and oxidative damage are highly related to cancer development and its treatment.

Inulin impacts tumorigenesis promotion by colibactin-producing in mice.

Introduction: The prebiotic inulin has previously shown both protective and tumor-promoting effects in colorectal cancer (CRC). These inconsistencies may be due to the gut microbial composition as several bacteria have been associated with CRC. Specifically, polyketide synthase-positive () promotes carcinogenesis and facilitates CRC progression through the production of colibactin, a genotoxin that induces double-strand DNA breaks (DSBs).

Pharmacokinetic Study of Intranasal Dexamethasone and Methylprednisolone Compared with Intravenous Administration: Two Open-Label, Single-Dose, Two-Period, Two-Sequence, Cross-Over Study in Healthy Volunteers.

Dexamethasone (DXM) and methylprednisolone (MEP) are potent glucocorticoids used to control several inflammatory conditions. Evidence of delayed DXM reaching the central nervous system (CNS) as well as tachyphylaxis and systemic, undesirable side effects are the main limitations of peripheral delivery. Intranasal administration offers direct access to the brain as it bypasses the blood-brain barrier.