The Microbiome Modulates the Immune System to Influence Cancer Therapy.

The gut microbiota composition can affect the tumor microenvironment and its interaction with the immune system, thereby having implications for treatment predictions. This article reviews the studies available to better understand how the gut microbiome helps the immune system fight cancer. To describe this fact, different mechanisms and approaches utilizing probiotics to improve advancements in cancer treatment will be discussed.

Molecular Insights of MAP4K4 Signaling in Inflammatory and Malignant Diseases.

Mitogen-activated protein kinase (MAPK) cascades are crucial in extracellular signal transduction to cellular responses. The classical three-tiered MAPK cascades include signaling through MAP kinase kinase kinase (MAP3K) that activates a MAP kinase kinase (MAP2K), which in turn induces MAPK activation and downstream cellular responses. The upstream activators of MAP3K are often small guanosine-5'-triphosphate (GTP)-binding proteins, but in some pathways, MAP3K can be activated by another kinase, which is known as a MAP kinase kinase kinase kinase (MAP4K).

Advancements in Cancer Immunotherapies.

Recent work has suggested involvement of the immune system in biological therapies specifically targeting tumor microenvironment. Substantial advancement in the treatment of malignant tumors utilizing immune cells, most importantly T cells that play a key role in cell-mediated immunity, have led to success in clinical trials. Therefore, this article focuses on the therapeutic approaches and developmental strategies to treat cancer.

CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT.

Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressing P. aeruginosa strains.

Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound.

Infection is a major co-morbidity that contributes to impaired healing in diabetic wounds. Although impairments in diabetic neutrophils have been blamed for this co-morbidity, what causes these impairments and whether they can be overcome, remain largely unclear. Diabetic neutrophils, isolated from diabetic individuals, exhibit chemotaxis impairment but this peculiar functional impairment has been largely ignored because it appears to contradict the clinical findings which blame excessive neutrophil influx as a major impediment to healing in chronic diabetic ulcers.

Therapeutic evaluation of immunomodulators in reducing surgical wound infection.

Despite many advances in infection control practices, including prophylactic antibiotics, surgical site infections (SSIs) remain a significant cause of morbidity, prolonged hospitalization, and death worldwide. Our innate immune system possesses a multitude of powerful antimicrobial strategies which make it highly effective in combating bacterial, fungal, and viral infections. However, pathogens use various stealth mechanisms to avoid the innate immune system, which in turn buy them time to colonize wounds and damage tissues at surgical sites.

IL-10 Dysregulation Underlies Chemokine Insufficiency, Delayed Macrophage Response, and Impaired Healing in Diabetic Wounds.

Persistent inflammation is a major contributor to healing impairment in diabetic chronic wounds. Paradoxically, diabetic wound environment during the acute phase of healing is completely different because it exhibits a reduced macrophage response owing to inadequate expression of CCL2 proinflammatory cytokine. What causes a reduction in CCL2 expression in diabetic wounds early after injury remains unknown.

Pseudomonas aeruginosa ExoT induces G1 cell cycle arrest in melanoma cells.

Recently, we demonstrated that Pseudomonas aeruginosa Exotoxin T (ExoT) employs two distinct mechanisms to induce potent apoptotic cytotoxicity in a variety of cancer cell lines. We further demonstrated that it can significantly reduce tumour growth in an animal model for melanoma. During these studies, we observed that melanoma cells that were transfected with ExoT failed to undergo mitosis, regardless of whether they eventually succumbed to ExoT-induced apoptosis or survived in ExoT's presence.

AKT-dependent sugar addiction by benzyl isothiocyanate in breast cancer cells.

The overall promise of breast cancer chemoprevention is exemplified by clinical success of selective estrogen receptor modulators and aromatase inhibitors. Despite clinical efficacy, these interventions have limitations, including rare but serious side effects and lack of activity against estrogen receptor-negative breast cancers. We have shown previously that dietary administration of benzyl isothiocyanate (BITC), which occurs naturally as a thioglucoside conjugate in edible cruciferous vegetables, inhibits development of estrogen receptor-negative breast cancer in mouse mammary tumor virus-neu (MMTV-neu) transgenic mice.

Disease Subtype-Independent Biomarkers of Breast Cancer Chemoprevention by the Ayurvedic Medicine Phytochemical Withaferin A.

Background: A nontoxic chemopreventive intervention efficacious against different subtypes of breast cancer is still a clinically unmet need. The present study was undertaken to determine the efficacy of an Ayurvedic medicine phytochemical (Withaferin A, [WA]) for chemoprevention of breast cancer and to elucidate its mode of action.

Methods: Chemopreventive efficacy of WA (4 and 8 mg/kg body weight) was determined using a rat model of breast cancer induced by N-methyl-N-nitrosourea (MNU; n = 14 for control group, n = 15 for 4 mg/kg group, and n = 18 for 8 mg/kg group).

Cutaneous exposure to clinically-relevant pigeon pea (Cajanus cajan) proteins promote T2-dependent sensitization and IgE-mediated anaphylaxis in Balb/c mice.

Epicutaneous (EC) sensitization to food allergens may occur when the skin has been lightly damaged. The study here tested whether cutaneous exposure to pigeon pea protein(s) may cause allergic sensitization. BALB/c mice were either orally gavaged or epicutaneously sensitized by repeated application of pigeon pea crude protein extract (CPE) on undamaged areas of skin without any adjuvant; afterwards, both groups were orally challenged with the pigeon pea CPE.

Mitochondrial dysfunction in cancer chemoprevention by phytochemicals from dietary and medicinal plants.

Cancer chemoprevention, a scientific term coined by Dr. Sporn in the late seventies, implies use of natural or synthetic chemicals to block, delay or reverse carcinogenesis. Phytochemicals derived from edible and medicinal plants have been studied rather extensively for cancer chemoprevention using preclinical models in the past few decades.

Benzanthrone induced immunotoxicity via oxidative stress and inflammatory mediators in Balb/c mice.

Benzanthrone (BA) is an important dye intermediate which is used in the manufacturing of several polycyclic vat and disperse dyes in textile industries. Several studies have indicated that the general population is also exposed to BA owing to its release from furnace effluents and automobile exhausts in the environment. In several clinical studies, it has been shown that workers exposed to BA developed itching, burning sensation, erythema and hyperpigmentation of the skin, which could be an outcome of the dysregulated immune response.

Elucidation of immediate type I reactions in native and GM mustard (Brassica spp.).

Mustard, a widely consumed spice can provoke allergic manifestations in mustard sensitive individuals. The aim of this study is to explore the allergenicity potential of GM mustard varieties (GM-V2 and GM-V4) having increased carotenoid content and compare it with the native (Varuna) and commercially available variety (Urvashi). Mustard protein sensitized (GM and non-GM) BALB/c mice sera were used to identify the allergenic proteins by IgE immunoblotting.

Toxicological mode of action of ZnO nanoparticles: Impact on immune cells.

The use of nanoscale materials is growing exponentially as concerns rise about the human hazards to it. It is assumed that living beings are coevolved with nanoparticles ever since the origin of life on earth and therefore, they must have developed the defense and toxicity mitigating mechanisms for nanoparticles. Although having peculiar properties these new materials also present new health risks upon interacting with biological systems.

Allergic manifestation by black gram (Vigna mungo) proteins in allergic patients, BALB/c mice and RBL-2H3 cells.

The prevalence of black gram (Vigna mungo) induced allergic reactions are reported from several parts of the world including Asia and Australia. But, a thorough exploration of the allergic reactions induced by black gram proteins is still lacking. Therefore, efforts have been made to explore black gram allergy using in vivo and in vitro approaches.

ZnO nanoparticles induced adjuvant effect via toll-like receptors and Src signaling in Balb/c mice.

Our previous studies indicated that zinc oxide nanoparticles (ZnO NPs) have adjuvant properties to a known allergen ovalbumin (OVA) in Balb/c mice. Therefore, in this study, we focused on the mechanisms involved in adjuvant responses induced by ZnO NPs. The eosinophil counts in the Peyers' patches of intestine and ICAM-1, Cox2 protein expressions were enhanced in the ZnO NPs/OVA group.

Phagocytic cells internalize ZnO particles by FcγII/III-receptor pathway.

The present study investigates the process of internalization for bulk ZnO particles in macrophages, and further elucidates the underlying mechanism. Since macrophages are active phagocytes and phagocytosis is a size dependent phenomenon, therefore we hypothesized that bulk ZnO may internalize into macrophages by phagocytic pathways. Interestingly, the phagocytic activity got enhanced in bulk ZnO treated macrophages.

Zinc oxide nanoparticles induce apoptosis by enhancement of autophagy via PI3K/Akt/mTOR inhibition.

Zinc oxide nanoparticles (ZnO NPs) induced macrophage cell death and its mechanism remains to be solved. Herein, we report that ZnO NPs induced ROS generation by depleting antioxidant enzymes, increasing lipid peroxidation and protein carbonyl contents in macrophages. The oxidative stress was induced by the inhibition of Nrf2 transcription factor release.