Melatonin and vitamin D as potential synergistic adjuvants for cancer therapy (Review).

Significant advancements have been made in cancer therapy; however, limitations remain with some conventional approaches. Adjuvants are agents used alongside primary treatments to enhance their efficacy and the treatment outcomes of patients. Modern lifestyles contribute to deficiencies in melatonin and vitamin D.

Melatonin regulates endoplasmic reticulum stress in diverse pathophysiological contexts: A comprehensive mechanistic review.

The endoplasmic reticulum (ER) is crucial for protein quality control, and disruptions in its function can lead to various diseases. ER stress triggers an adaptive response called the unfolded protein response (UPR), which can either restore cellular homeostasis or induce cell death. Melatonin, a safe and multifunctional compound, shows promise in controlling ER stress and could be a valuable therapeutic agent for managing the UPR.

Brain washing and neural health: role of age, sleep, and the cerebrospinal fluid melatonin rhythm.

The brain lacks a classic lymphatic drainage system. How it is cleansed of damaged proteins, cellular debris, and molecular by-products has remained a mystery for decades. Recent discoveries have identified a hybrid system that includes cerebrospinal fluid (CSF)-filled perivascular spaces and classic lymph vessels in the dural covering of the brain and spinal cord that functionally cooperate to remove toxic and non-functional trash from the brain.

Melatonin modulates the Warburg effect and alters the morphology of hepatocellular carcinoma cell line resulting in reduced viability and migratory potential.

Aims: Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating HCC. We aimed to study in HuH 7.

Melatonin Reverses the Warburg-Type Metabolism and Reduces Mitochondrial Membrane Potential of Ovarian Cancer Cells Independent of MT1 Receptor Activation.

Ovarian cancer (OC) is the most lethal gynecologic malignancy, and melatonin has shown various antitumor properties. Herein, we investigated the influence of melatonin therapy on energy metabolism and mitochondrial integrity in SKOV-3 cells and tested whether its effects depended on MT1 receptor activation. SKOV-3 cells were exposed to different melatonin concentrations, and experimental groups were divided as to the presence of MT1 receptors (melatonin groups) or receptor absence by RNAi silencing (siRNA MT1+melatonin).

Melatonin: A mitochondrial resident with a diverse skill set.

Melatonin is an ancient molecule that originated in bacteria. When these prokaryotes were phagocytized by early eukaryotes, they eventually developed into mitochondria and chloroplasts. These new organelles retained the melatonin synthetic capacity of their forerunners such that all present-day animal and plant cells may produce melatonin in their mitochondria and chloroplasts.

The proteomic landscape of ovarian cancer cells in response to melatonin.

Ovarian cancer (OC) is the most lethal gynecological malignancy with a highly negative prognosis. Melatonin is an indoleamine secreted by the pineal gland during darkness and has shown antitumor activity in both in vitro and in vivo experiments. Herein, we investigated the influence of melatonin on the proteome of human ovarian carcinoma cells (SKOV-3 cell line) using the Ultimate 3000 LC Liquid NanoChromatography equipment coupled to a Q-Exactive mass spectrometry.

Aging whole blood transcriptome reveals candidate genes for SARS-CoV-2-related vascular and immune alterations.

The risk of severe COVID-19 increases with age as older patients are at highest risk. Thus, there is an urgent need to identify how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with blood components during aging. We investigated the whole blood transcriptome from the Genotype-Tissue Expression (GTEx) database to explore differentially expressed genes (DEGs) translated into proteins interacting with viral proteins during aging.

Caffeine consumption attenuates ethanol-induced inflammation through the regulation of adenosinergic receptors in the UChB rats cerebellum.

Caffeine consumption is able to interfere in cellular processes related to inflammatory mechanisms by acting through the adenosinergic system. This study aimed to recognize alterations related to adenosinergic system and inflammatory process in the cerebellum of University of Chile Bibulous (UChB) rats after the consumption of ethanol and caffeine. UChB and Wistar rats, males at 5 months old, were divided into the groups ( = 15/group): (i) Control (Wistar rats receiving water); (ii) Ethanol group (UChB rats receiving ethanol solution at 10%) and (iii) Ethanol+caffeine group (UChB rats receiving ethanol solution at 10% added of 3 g/L of caffeine).

Nandrolone decanoate causes uterine injury by changing hormone levels and sex steroid receptors in a dose- and time-dependent manner.

Different doses of nandrolone decanoate (ND) were used to investigate the expression of uterine sex steroid receptors (AR, ER-α, and ER-β) and the levels of serum sex hormones after treatment and recovery periods in adult rats. ND doses of 1.87, 3.

Protein restriction during puberty alters nutritional parameters and affects ovarian and uterine histomorphometry in adulthood in rats.

In a large part of the population inefficient ingestion of proteins, whether for cultural, aesthetic or economic reasons, is a global concern. Low-protein diets can cause severe functional complications, mainly during the development and maturation of organs and systems, including the female reproductive system. The present study investigated the effect of nutritional protein restriction during puberty on the oestrous cycle and expression of sex steroid receptors (AR, ERα e ERβ) in ovarian and uterine tissues of adult rats.

Pterostilbene influences glycemia and lipidemia and enhances antioxidant status in the liver of rats that consumed sucrose solution.

Aims: The present study investigated the potential effects of pterostilbene (PT) on glycemic and lipid profiles, fat storage, cardiovascular indices, and hepatic parameters of rats fed with sucrose solution.

Main Methods: 24 male Wistar rats received either drinking water or a 40% sucrose solution over a period of 140 days. After this period, animals were randomly allocated into four groups (n = 6): Control (C), C + Pterostilbene (PT), Sucrose (S), and S + PT.

Maternal protein restriction impairs nutrition and ovarian histomorphometry without changing p38MAPK and PI3K-AKT-mTOR signaling in adult rat ovaries.

Aims: Because an adequate protein supply is detrimental for the maintenance of folliculogenesis and ovulation, we evaluated the impact of maternal low protein diet on nutritional parameters, estrous cycle, ovarian histomorphometry, and on the expression of metabolic and survival signaling molecules in different follicular stages.

Main Methods: Twenty Wistar pregnant rats were divided into two groups: the normoprotein (NP) group, composed of animals that received 17% protein, and a low-protein (LP) group, composed of animals that received 6% protein during gestation and lactation period. After weaning, female rats were fed with standard diet until the 120-days-old.

P-MAPA activates TLR2 and TLR4 signaling while its combination with IL-12 stimulates CD4+ and CD8+ effector T cells in ovarian cancer.

Aims: Ovarian cancer (OC) is the most lethal gynecological malignancies and many women develop chemoresistance associated with the inflammatory process. We investigated the effects of P-MAPA and IL-12 on the inflammatory and immune responses in a chemically-induced OC model.

Main Methods: OCs were induced with 7,12-dimethylbenz(a)anthracene into the ovarian bursa, and the animals were given P-MAPA (5 mg/kg bw.

Long-term sucrose solution consumption causes metabolic alterations and affects hepatic oxidative stress in Wistar rats.

As the number of overweight and obese people has risen in recent years, there has been a parallel increase in the number of people with metabolic syndrome, diabetes and non-alcoholic fatty liver disease. The consumption of artificially sweetened beverages contributes to these epidemics. This study investigated the long-term effects of ingestion of a 40% sucrose solution on serum and hepatic parameters in male Wistar rats ().

The role of Toll-like receptor 4 signaling pathway in ovarian, cervical, and endometrial cancers.

Toll-like receptors (TLRs) are critical sensors related to inflammation and tumorigenesis. Among all subtypes, the TLR4 is a highly described transmembrane protein involved in the inflammatory process. The TLR4/myeloid differentiation factor 88 (MyD88) signaling pathway has been implicated in oncogenic events in several tissues and is associated with survival of patients.

Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate.

Background: Altered lipid metabolism is an important characteristic of neoplastic cells, with androgens and growth factors being major regulatory agents of the lipid metabolism process. We investigated the effect of physical resistance training on lipid metabolism and apoptosis in the adult Wistar rat prostate.

Methods: Two experimental groups represented sedentary and physical resistance training.

Melatonin inhibits Warburg-dependent cancer by redirecting glucose oxidation to the mitochondria: a mechanistic hypothesis.

Melatonin has the ability to intervene in the initiation, progression and metastasis of some experimental cancers. A large variety of potential mechanisms have been advanced to describe the metabolic and molecular events associated with melatonin's interactions with cancer cells. There is one metabolic perturbation that is common to a large number of solid tumors and accounts for the ability of cancer cells to actively proliferate, avoid apoptosis, and readily metastasize, i.

Maternal protein restriction differentially alters the expression of AQP1, AQP9 and VEGFr-2 in the epididymis of rat offspring.

Background: Maternal protein restriction causes sperm alterations in the offspring, most of which are associated with epididymal functions. Because fluid reabsorption/secretion dynamics in the epididymal environment play important roles in the process of sperm maturation and concentration, we investigated the effects of maternal protein restriction on the expression of aquaporins (AQP1 and AQP9), vascular endothelial growth factor (VEGFa), and its receptor VEGFr-2 in different stages of postnatal epididymal development.

Methods: Pregnant rats were divided into groups that received normoprotein (17% protein) and low-protein diets (6% protein) during gestation and lactation.

Mitochondrial functions and melatonin: a tour of the reproductive cancers.

Cancers of the reproductive organs have a strong association with mitochondrial defects, and a deeper understanding of the role of this organelle in preneoplastic-neoplastic changes is important to determine the appropriate therapeutic intervention. Mitochondria are involved in events during cancer development, including metabolic and oxidative status, acquisition of metastatic potential, resistance to chemotherapy, apoptosis, and others. Because of their origin from melatonin-producing bacteria, mitochondria are speculated to produce melatonin and its derivatives at high levels; in addition, exogenously administered melatonin accumulates in the mitochondria against a concentration gradient.

Histopathological changes in androgenized ovaries are recovered by melatonin treatment.

Nandrolone decanoate (ND) is a synthetic steroid, which promotes adverse effects on the ovarian tissue, and melatonin (MLT) exhibits a number of beneficial properties in the reproductive system. This study evaluated the general features of the ovarian tissue and the immunoexpression of sex steroid receptors in ND-treated rats that were submitted to short-term melatonin treatment. Adult rats received mineral oil (control group) and ND at doses of 7.

P-MAPA immunotherapy potentiates the effect of cisplatin on serous ovarian carcinoma through targeting TLR4 signaling.

Background: Toll-like receptors (TLRs) are transmembrane proteins expressed on the surface of ovarian cancer (OC) and immune cells. Identifying the specific roles of the TLR-mediated signaling pathways in OC cells is important to guide new treatments. Because immunotherapies have emerged as the adjuvant treatment for patients with OC, we investigated the effect of a promising immunotherapeutic strategy based on protein aggregate magnesium-ammonium phospholinoleate-palmitoleate anhydride (P-MAPA) combined with cisplatin (CIS) on the TLR2 and TLR4 signaling pathways via myeloid differentiation factor 88 (MyD88) and TLR-associated activator of interferon (TRIF) in an in vivo model of OC.

Ovarian sex steroid receptors and sex hormones in androgenized rats.

This study evaluated for the first time the effects of different doses of the anabolic steroid nandrolone decanoate (ND) on the expression of ovarian steroid receptors (AR, ER-α (ESR1) and ER-β (ESR2)) and related sex hormones after treatment and recovery periods in adult rats. The animals were injected subcutaneously with doses of ND (1.87, 3.

Effects of different doses of nandrolone decanoate on estrous cycle and ovarian tissue of rats after treatment and recovery periods.

This study tested the hypothesis that different doses of nandrolone decanoate (ND) will cause changes in the estrous cycle and ovarian tissue of adult rats; and investigated the duration of the recovery period that is sufficient to restore the damage in the animals treated with different doses. Wistar rats were treated with ND at doses of 1.87, 3.