Peanut Shell Extract Improves Markers of Glucose Homeostasis in Diabetic Mice by Modulating Gut Dysbiosis and Suppressing Inflammatory Immune Response.

Background/objective: There is strong evidence that the tripartite interaction between glucose homeostasis, gut microbiota, and the host immune system plays a critical role in the pathophysiology of type 2 diabetes mellitus (T2DM). We reported previously that peanut shell extract (PSE) improves mitochondrial function in db/db mice by suppressing oxidative stress and inflammation in the liver, brain, and white adipose tissue. This study evaluated the impacts of PSE supplementation on glucose homeostasis, liver histology, intestinal microbiome composition, and the innate immune response in diabetic mice.

Beneficial Effects of Ginger Root Extract on Pain Behaviors, Inflammation, and Mitochondrial Function in the Colon and Different Brain Regions of Male and Female Neuropathic Rats: A Gut-Brain Axis Study.

Background: Neuroinflammation and mitochondrial dysfunction have been implicated in the progression of neuropathic pain (NP) but can be mitigated by supplementation with gingerol-enriched ginger (GEG). However, the exact benefits of GEG for each sex in treating neuroinflammation and mitochondrial homeostasis in different brain regions and the colon remain to be determined.

Objective: Evaluate the effects of GEG on emotional/affective pain and spontaneous pain behaviors, neuroinflammation, as well as mitochondria homeostasis in the amygdala, frontal cortex, hippocampus, and colon of male and female rats in the spinal nerve ligation (SNL) NP model.

Peanut Shell Extract Improves Mitochondrial Function in db/db Mice via Suppression of Oxidative Stress and Inflammation.

Accumulating evidence shows a strong correlation between type 2 diabetes mellitus, mitochondrial dysfunction, and oxidative stress. We evaluated the effects of dietary peanut shell extract (PSE) supplementation on mitochondrial function and antioxidative stress/inflammation markers in diabetic mice. Fourteen db/db mice were randomly assigned to a diabetic group (DM in AIN-93G diet) and a PSE group (1% wt/wt PSE in AIN-93G diet) for 5 weeks.

Ginger Polyphenols Reverse Molecular Signature of Amygdala Neuroimmune Signaling and Modulate Microbiome in Male Rats with Neuropathic Pain: Evidence for Microbiota-Gut-Brain Axis.

Emerging evidence shows that the gut microbiota plays an important role in neuropathic pain (NP) via the gut-brain axis. Male rats were divided into sham, spinal nerve ligation (SNL), SNL + 200 mg GEG/kg BW (GEG200), and SNL + 600 mg GEG/kg BW (GEG600) for 5 weeks. The dosages of 200 and 600 mg GEG/kg BW for rats correspond to 45 g and 135 g raw ginger for human daily consumption, respectively.

Ginger alleviates mechanical hypersensitivity and anxio-depressive behavior in rats with diabetic neuropathy through beneficial actions on gut microbiome composition, mitochondria, and neuroimmune cells of colon and spinal cord.

The relationship among gut microbiota, mitochondrial dysfunction/neuroinflammation, and diabetic neuropathic pain (DNP) has received increased attention. Ginger has antidiabetic and analgesic effects because of its anti-inflammatory property. We examined the effects of gingerols-enriched ginger (GEG) supplementation on pain-associated behaviors, gut microbiome composition, and mitochondrial function and neuroinflammation of colon and spinal cord in DNP rats.

Turmeric Bioactive Compounds Alleviate Spinal Nerve Ligation-Induced Neuropathic Pain by Suppressing Glial Activation and Improving Mitochondrial Function in Spinal Cord and Amygdala.

This study examined the effects of turmeric bioactive compounds, curcumin C3 complex® (CUR) and bisdemethoxycurcumin (BDMC), on mechanical hypersensitivity and the gene expression of markers for glial activation, mitochondrial function, and oxidative stress in the spinal cord and amygdala of rats with neuropathic pain (NP). Twenty-four animals were randomly assigned to four groups: sham, spinal nerve ligation (SNL, an NP model), SNL+100 mg CUR/kg BW p.o.

A High Dose of Calcitriol Inhibits Glycolysis and M2 Macrophage Polarization in the Tumor Microenvironment by Repressing mTOR Activation: in vitro and Molecular Docking Studies.

Background/aims: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of cancer and the growth of tumors. Thus, modulating macrophages-cancer cells interaction in the TME may be therapeutically beneficial.

Ginger Root Extract Improves GI Health in Diabetic Rats by Improving Intestinal Integrity and Mitochondrial Function.

Background Emerging research suggests hyperglycemia can increase intestinal permeability. Ginger and its bioactive compounds have been reported to benefit diabetic animals due to their anti-inflammatory and antioxidant properties. In this study, we revealed the beneficial effect of gingerol-enriched ginger (GEG) on intestinal health (i.

Gingerol-Enriched Ginger Supplementation Mitigates Neuropathic Pain Mitigating Intestinal Permeability and Neuroinflammation: Gut-Brain Connection.

Emerging evidence suggests an important role of the gut-brain axis in the development of neuropathic pain (NP). We investigated the effects of gingerol-enriched ginger (GEG) on pain behaviors, as well as mRNA expressions of inflammation tight junction proteins in GI tissues (colon) and brain tissues (amygdala, both left and right) in animals with NP. Seventeen male rats were randomly divided into three groups: Sham, spinal nerve ligation (SNL, pain model), and SNL+0.

Parthenolide reverses the epithelial to mesenchymal transition process in breast cancer by targeting TGFbeta1: In vitro and in silico studies.

Aims: Breast cancer metastasis is the leading cause of mortality among breast cancer patients. Epithelial to mesenchymal transition (EMT) is a biological process that plays a fundamental role in facilitating breast cancer metastasis. The present study assessed the efficacy of parthenolide (PTL Tanacetum parthenium) on EMT and its underlying mechanisms in both lowly metastatic, estrogen-receptor positive, MCF-7 cells and highly metastatic, triple-negative MDA-MB-231 cells.

VD and LXR agonist (T0901317) combination demonstrated greater potency in inhibiting cholesterol accumulation and inducing apoptosis via ABCA1-CHOP-BCL-2 cascade in MCF-7 breast cancer cells.

Obesity is associated with hypercholesterolemia and is a global epidemic. Epidemiological and animal studies revealed cholesterol is an essential regulator of estrogen receptor positive (ER+) breast cancer progression while inhibition of cholesterol accumulation was found to prevent breast tumor growth. Individually, vitamin D and LXR agonist T0901317 showed anticancer properties.

Higher Glucose Enhances Breast Cancer Cell Aggressiveness.

Cancer cells overexpress several transcription factors and motor proteins, such as NFkB and kinesin, to accommodate their high energy demand as well as migratory needs via enhanced glycolysis. We hypothesize that high glucose drives cancer progression and cell aggressiveness by decreasing actin expression, increasing NFkB, and kinesin expressions, and by activating Epithelial Mesenchymal Transition (EMT). Using lowly metastatic MCF-7 and highly metastatic MDA-MB231 (MB231) breast cancer cells - highly incident cancer types - we establish how glucose metabolism regulates actin and the biochemical changes that lead to alterations of cell mechanical properties.

Enhanced blebbing as a marker for metastatic prostate cancer.

Highly metastatic prostate cancer cells flowing through a microfluidic channel form plasma membrane blebs: they form 27% more than normal cells and have a lower stiffness (about 50%). Hypo-osmotic stress assays (with osmolarity) show 22% more blebbing of highly metastatic than moderately metastatic and 30% more than normal cells. Plasma membrane blebbing is known to provide important metastatic capabilities to cancer cells by aiding cell detachment from the primary tumor site and increasing cell deformability to promote cell migration through the extracellular matrix.

VD mitigates breast cancer aggressiveness by targeting V-H-ATPase.

Low vitamin D levels increase the risk of developing several cancer types including breast cancer. Breast cancer is the most incident cancer among women worldwide and in the United States. Our previous study showed that vitamin D (VD) decreases breast cancer aggressiveness by inhibiting mammalian target of rapamycin (mTOR).

Myrtenal-induced V-ATPase inhibition - A toxicity mechanism behind tumor cell death and suppressed migration and invasion in melanoma.

Background: Metastatic tumor cells have acidic extracellular pH and differential electrochemical H gradients generated across their cell membranes by V-type H-ATPases. This study shows that inhibition of the V-ATPases by the plant-derived monoterpene Myrtenal results in tumor cell death and decreased metastatic dissemination in mice.

Methods: The Myrtenal anticancer toxicity was evaluated in vitro using murine (B16F0 and B16F10) and human (SkMel-5) melanoma cell lines, and in in vivo mouse metastatic dissemination model.

Aggressive prostate cancer cell nuclei have reduced stiffness.

It has been hypothesized that highly metastatic cancer cells have softer nuclei and hence would travel faster through confining environments. Our goal was to prove this untested hypothesis for prostate cells. Our nuclear creep experiments using a microfluidic channel with a narrow constriction show that stiffness of aggressive immortalized prostate cancer nuclei is significantly lower than that of immortalized normal cell nuclei and hence can be a convenient malignancy marker.

Vitamin D decreases glycolysis and invasiveness, and increases cellular stiffness in breast cancer cells.

Breast cancer is one of the major causes of death in the USA. Cancer cells, including breast, have high glycolysis rates to meet their energy demands for survival and growth. Vitamin D (VD) is important for many important physiological processes such as bone mineralization, but its anticancer role is yet to be proven.

Vacuolar H+-ATPase in the nuclear membranes regulates nucleo-cytosolic proton gradients.

The regulation of the luminal pH of each organelle is crucial for its function and must be controlled tightly. Nevertheless, it has been assumed that the nuclear pH is regulated by the cytoplasmic proton transporters via the diffusion of H across the nuclear pores because of their large diameter. However, it has been demonstrated that ion gradients exist between cytosol and nucleus, suggesting that the permeability of ions across the nuclear pores is restricted.