Hormetic effect of low doses of rapamycin triggers anti-aging cascades in WRL-68 cells by modulating an mTOR-mitochondria cross-talk.

Background: Rapamycin is hormetic in nature-it demonstrates contrasting effects at high and low doses. It is toxic at moderate/high doses, while it can restrain aging and extend lifespan at low doses. However, it is not fully understood how rapamycin governs cellular aging.

Microtubule motors in centrosome homeostasis: A target for cancer therapy?

Cancer is a grievous concern to human health, owing to a massive heterogeneity in its cause and impact. Dysregulation (numerical, positional and/or structural) of centrosomes is one of the notable factors among those that promote onset and progression of cancers. In a normal dividing cell, a pair of centrosomes forms two poles, thereby governing the formation of a bipolar spindle assembly.

Friend turned foe: A curious case of disrupted endosymbiotic homeostasis promoting the Warburg effect in sepsis.

Sepsis is a grievous health concern with limited understanding of its precise etiology. Although studies on sepsis have implicated the Warburg effect (mitigation of mitochondrial oxidative phosphorylation, as evident from aerobic glycolysis), we propose that an evolutionary perspective might further unravel its etiology. The endosymbiotic theory suggests that evolution of a eukaryotic cell is a consequence of the fruitful association between an archaea (Asgard) and an alphaproteobacterium (Rickettsia).

Hexavalent chromium-induced autophagic death of WRL-68 cells is mitigated by aqueous extract of L. seeds.

In this study, we assessed the potential of aqueous extract (CSE) of L. (cumin) seeds in protecting WRL-68 cells from hexavalent chromium [Cr(VI)]-induced oxidative injury. Cells exposed to Cr(VI) (10 μM CrO) for 24 h demonstrated a twofold increase in ROS, which, in turn, led to extensive oxidative stress, consequently causing colossal decline in cell viability (by 58.

Gene therapy for the mitochondrial genome: Purging mutations, pacifying ailments.

In the recent years, the reported cases of mitochondrial disorders have reached a colossal number. These disorders spawn a sundry of pathological conditions, which lead to pernicious symptoms and even fatality. Due to the unpredictable etiologies, mitochondrial diseases are putatively referred to as "mystondria" (mysterious diseases of mitochondria).

Cancer chemotherapeutics in rheumatoid arthritis: A convoluted connection.

Chemotherapy is one of the most popular therapeutic strategies to treat cancer. However, cancer chemotherapeutics have often been associated with impairment of the immune system, which might consequently lead to an augmented risk of autoimmune disorders, such as rheumatoid arthritis. Though the accurate mechanistic facets of rheumatoid arthritis induction have not been interpreted yet, a conglomeration of genetic and environmental factors might promote its etiology.

Cancer nanotheranostics: Strategies, promises and impediments.

Cancer has remained one of the most indomitable conundrums for scientists over centuries due to its multifarious etiology. While improved therapeutic and diagnostic approaches have commendably augmented the rate of survival of cancer patients, a holistic riddance from the ailment is still implausible. Hence, further explorations to scout for novel strategies of cancer therapy and diagnosis are necessary.

Designing a broad-spectrum integrative approach for cancer prevention and treatment.

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.

A multi-targeted approach to suppress tumor-promoting inflammation.

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity.

Novel Pactamycin Analogs Induce p53 Dependent Cell-Cycle Arrest at S-Phase in Human Head and Neck Squamous Cell Carcinoma (HNSCC) Cells.

Pactamycin, although putatively touted as a potent antitumor agent, has never been used as an anticancer drug due to its high cytotoxicity. In this study, we characterized the effects of two novel biosynthetically engineered analogs of pactamycin, de-6MSA-7-demethyl-7-deoxypactamycin (TM-025) and 7-demethyl-7-deoxypactamycin (TM-026), in head and neck squamous cell carcinoma (HNSCC) cell lines SCC25 and SCC104. Both TM-025 and TM-026 exert growth inhibitory effects on HNSCC cells by inhibiting cell proliferation.

Broad targeting of resistance to apoptosis in cancer.

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer.

Sustained proliferation in cancer: Mechanisms and novel therapeutic targets.

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth.

Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition.

Genomic instability can initiate cancer, augment progression, and influence the overall prognosis of the affected patient. Genomic instability arises from many different pathways, such as telomere damage, centrosome amplification, epigenetic modifications, and DNA damage from endogenous and exogenous sources, and can be perpetuating, or limiting, through the induction of mutations or aneuploidy, both enabling and catastrophic. Many cancer treatments induce DNA damage to impair cell division on a global scale but it is accepted that personalized treatments, those that are tailored to the particular patient and type of cancer, must also be developed.

Cancer prevention and therapy through the modulation of the tumor microenvironment.

Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adaptive immunity.

Immune evasion in cancer: Mechanistic basis and therapeutic strategies.

Cancer immune evasion is a major stumbling block in designing effective anticancer therapeutic strategies. Although considerable progress has been made in understanding how cancers evade destructive immunity, measures to counteract tumor escape have not kept pace. There are a number of factors that contribute to tumor persistence despite having a normal host immune system.

Influence of Rituximab on Central Nervous System Relapse in Diffuse Large B-Cell Lymphoma and Role of Prophylaxis--A Systematic Review of Prospective Studies.

Despite the improvement in overall survival in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era, the occurrence of central nervous system (CNS) relapse heralds a very poor prognosis. The evidence is conflicting on the incidence and pattern of CNS relapse in the rituximab era compared with before the rituximab era and on the role of CNS prophylaxis. We conducted a systematic analysis of the data from 7 prospective studies, studying the incidence and type of CNS relapse, the role of prophylaxis, and survival after CNS relapse, with and without rituximab-based chemotherapy.

Broad targeting of angiogenesis for cancer prevention and therapy.

Deregulation of angiogenesis--the growth of new blood vessels from an existing vasculature--is a main driving force in many severe human diseases including cancer. As such, tumor angiogenesis is important for delivering oxygen and nutrients to growing tumors, and therefore considered an essential pathologic feature of cancer, while also playing a key role in enabling other aspects of tumor pathology such as metabolic deregulation and tumor dissemination/metastasis. Recently, inhibition of tumor angiogenesis has become a clinical anti-cancer strategy in line with chemotherapy, radiotherapy and surgery, which underscore the critical importance of the angiogenic switch during early tumor development.

CNS Hemangiopericytoma: A Systematic Review of 523 Patients.

Background: Central nervous system (CNS) hemangiopericytomas are rare mesenchymal tumors of the brain. In the absence of randomized clinical trials or large studies, the only information we have about the natural history and the management is from isolated clinical case series. They have suggested that surgery is beneficial, with conflicting results on the role of complete resection and adjuvant radiation.

Selective ablation of Ctip2/Bcl11b in epidermal keratinocytes triggers atopic dermatitis-like skin inflammatory responses in adult mice.

Background: Ctip2 is crucial for epidermal homeostasis and protective barrier formation in developing mouse embryos. Selective ablation of Ctip2 in epidermis leads to increased transepidermal water loss (TEWL), impaired epidermal proliferation, terminal differentiation, as well as altered lipid composition during development. However, little is known about the role of Ctip2 in skin homeostasis in adult mice.

Comparing newer oral anti-platelets prasugrel and ticagrelor in reduction of ischemic events-evidence from a network meta-analysis.

The two newer antiplatelet drugs, prasugrel and ticagrelor have both been incorporated in various national guidelines and are both under consideration for approval or have already been approved by various drug regulatory authorities. Mortality benefits with clopidogrel were comparable to newer anti-platelets, and prasugrel had great anti-ischemic potency than ticagrelor. We searched PubMed, EMBASE and Cochrane Central Register of Controlled Trials' databases for randomized controlled trials conducted between 1990 and 2012 that assessed clinical outcomes with prasugrel or ticagrelor.

Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis.

Background: COUP-TF interacting protein 2 [(Ctip2), also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/-) mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB) establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/-)) mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing.

Pre-procedural Elevated White Blood Cell Count and Neutrophil-Lymphocyte (N/L) Ratio are Predictors of Ventricular Arrhythmias During Percutaneous Coronary Intervention.

Aims: The absolute white blood cell (WBC) count and neutrophil to lymphocyte (N/L) ratio are predictors of death/myocardial infarction in patients who have undergone coronary angiography. We hypothesized that a pre-procedural elevated WBC count and an elevated N/L ratio would be a predictor of development of significant ventricular arrhythmias in subjects undergoing percutaneous coronary intervention (PCI).

Methods And Results: We retrieved the data for all patients developing ventricular arrhythmia during PCI between 1999 to 2009 from our cath lab database (from 30,798 records), a total of 70 patients (Group I), and tabulated their WBC counts and absolute neutrophil and lymphocyte counts as well as N/L ratios.