Comment on "renal denervation for hypertension".

We have attentively reviewed the article "Renal Denervation for Hypertension" and commend the author's dedication to addressing this intricate subject. However, we wish to highlight a few points that, in our assessment, could enhance the overall quality of the article.

Rare case image of retroperitoneal metastases from breast primary.

Breast cancer remains the leading cause of cancer related death in females worldwide. Metastatsis from breast primary are usually seen in lungs, bones and liver. Uncommon sites include adrenals, thyroid, spleen, pancreas and urinary bladder. Retroperitoneal metastasis are considered most unsual among breast cancer. We present the case of a treated breast cancer patient with a large reteroperitoneal lesion suggesting other aetiologies on imaging but proved to be metastasis on histopathology.

The impact of airborne pollution and exposure to solar ultraviolet radiation on skin: mechanistic and physiological insight.

For several decades air pollution has been recognized to hit drastically the skin of human body. Air pollutants predominantly accountable for aging, oxidative damage, and inflammatory allergic reactions led to psoriasis, dermatitis, acne, and skin cancer owing to the impaired functions of DNA, proteins, and lipid biomolecules. Elevated air pollution and its detrimental effects along with variations in physiological parameters of the skin are verily the scaffold for anti-pollution assertions and could be recognized as markers. The present article encompasses the salient features of air pollution and UV radiations besides dreadful effects on human skin physiological parameters and some anti-pollution approaches.

Why do patients with limb ischaemia present late to a vascular surgeon? A prospective cohort study from the developing world.

OBJECTIVE: To look into the factors responsible for delay in presentation of Iimb ischemia patients to a vascular surgeon. Methods: The prospective cohort study was conducted at the Aga Khan University Hospital, Karachi, from October 01, 2016, to August 10, 2018. Patients coming with delayed presentation of both acute and chronic limb ischemia were included. All the patients were assessed by qualified vascular surgeons. SPSS 23 was used for data analysis. Results: Of the 55 patients, 33(60%) had acute and 22(40%) had chronic limb ischaemia. Mean age of acute cases was 44±23.72 years and it was 60±12.49 years for chronic cases. Overall, the commonest reason behind delay was non-referral by primary physician which was the case with 11(33.3%) patients in the acute group, and 13(59%) in the chronic group. The limb loss in the acute group was 20(60%) and 8(36%) in the chronic group.. Conclusion: Delayed presentation of patients with limb ischaemia is mainly due to non-referral. A robust campaign needs to be launched to reduce the rate of limb loss.

TRPC signaling mechanisms and therapeutic opportunities: trapdoors are monitored by gatekeepers.

This Review summarizes our current state of knowledge of the functional role of TRPC channels in health and disease, with particular emphasis on current advancements in the field. Additionally, this Review provides an up-to-date summary of SKF-96365 acting on TRPC channels, and discusses strategies to further investigate the potential of these channels for therapeutic intervention.

Breakpoint cluster region-c-abl oncogene 1, non-receptor tyrosine kinase signaling: current patterns of the versatile regulator revisited.

Increasing sophisticated information suggests that cancer cells express constitutively active oncogenic kinases such as breakpoint cluster region- c-abl oncogene 1, non-receptor tyrosine kinase (BCR-ABL1) that promote carcinogenesis independent of extrinsic growth factors. It is a well-established fact that through the aberrant activation of BCR-ABL1 signal transduction cascade, the perception of cellular growth signals becomes disconnected from the processes promoting cell growth, and this underlies the pathophysiology of leukemia. In this particular review we discuss the oncogenes and tumor suppressors comprising the regulatory network upstream and downstream of BCR-ABL1 and dismantle how derailed BCR-ABL1 signaling provides cell a selective growth advantage. Besides, we discuss why activation of BCR-ABL1, as an outcome of distinct oncogenic events, results in miscellaneous clinical outcomes, and how the intricacy of the BCR-ABL1 signaling network might dictate therapeutic approaches. In this review, our current comprehension of BCR-ABL1 signaling will be summarized.

Prostate cancer is known by the companionship with ATM and miRNA it keeps: craftsmen of translation have dual behaviour with tailors of life thread.

Research on prostate cancer progression has focused extensively on the concept of miRNA, which can operate either as promoters or as suppressors of carcinogenesis. Moreover, recent genetic studies and emerging functional work show that strikingly similar and overlapping pathways are involved in prostate carcinogenesis. Unswervingly, these elements constitute a recently explored 'network of networks' that dynamically reorganizes during DNA damage and is responsible for positively or negatively regulating genome organization and integrity. We consider these facets of convergence and discuss how insights from diametrically opposed interactions of ataxia-telangiectasia mutated and mitrons can inform us about, and possibly help us to get a step closer to personalized medicine.

NutriTRAILomics in prostate cancer: time to have two strings to one's bow.

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype. The purpose of this review is to significantly inspect results from current research concerning the mechanisms of action of phytonutrients and potential effects on prostate cancer. Substantial emerging data supports the synergistic adiministration of nutraceuticals with TRAIL in prostate cancer progression to circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods for discovery, validation, characterization and standardization of these multicomponent phyto-therapeutics is vital to their recognition into mainstream medicine. The key to interpret a personalized response is a greater comprehension of nutrigenomics, proteomics and metabolomics.

Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation.

OBJECTIVE: Prostate cancer is a polyfactorial molecular anomaly that is offering refractoriness against a broad range of therapeutic drugs. Growth factor receptors are actively implicated in oncogenesis. PDGFR/EGFR mediated exacerbated signaling has a central participation and is contributory in fueling the signal transductions that gear up prostate cancer progression. MATERIALS AND METHODS: In this particular study, androgen sensitive, Prostate cancer cell line (LNCaP) was used. Pretreatment of cell line with PDGF resulted in an enhanced proliferation of cells which was evaluated by MTT assay. Treatment of cell line with either alone Curcumin, EGCG, sulforaphane or in combination was evaluated. PDGFR/EGFR activation (phosphorylation) was studied using western blot. RESULTS: Results indicated that phosphorylation was gradually downregulated after treatment with individual compound. However there was a remarkable decrease in cellular proliferation after a combinatorial approach which is indicative of the fact that PDGFR phosphorylation was decreased outstandingly as evaluated by MTT assay. That also gave a prominent decline in the expression and subsequent decrease in proliferation pattern of cells. CONCLUSION: Despite the fact that little is still known regarding the mechanistic insights by which phytonutrients act as barrier to cancer, and attempts to translate the studies from benchtop to bedside are in progress. A detailed analysis of nutraceuticals will help a lot in identifying the stumbling blocks in the standardization of therapeutic interventions.

TRPM channels: same ballpark, different players, and different rules in immunogenetics.

Transient receptor potential (TRP) channels belong to a large family of cation channels and are the "border guards" predominantly localized to the plasma membrane. Research over the years has considerably and highly developed the knowledge of expression and functional aspects of the TRPM channels. A closer look at the channel dynamics has dismantled undeniable substantiation for multifaceted roles for TRPM channel-mediated extracellular Ca(2+) influx in several physiological and pathophysiological functions. Given the wealth of literature unfolding the multiple roles of TRP channels in physiology in a very extensive range of different mammalian tissues, this review confines itself to the literature describing the multiple roles of TRPM channels in diabetes, smooth muscle cell regulation, immunological responses, and emerging aspects of cancer. We also focus on differential activities of TRPM channels after post-transcriptional and post-translational processing and their exquisite roles at various cellular and molecular levels.

SMURF and NEDD4: sharp shooters monitor the gate keepers and ion traffic controllers of lead astray cell.

It is becoming increasingly apparent that a complex bar code underlies the quantitative aspects of extracellular signal regulation. Cell type-specific and context-dependent transcriptional programs are triggered by sophisticated nanomachinery consisting of HECT enzymes which monitor signal generation, transduction and termination. How the HECT enzymes safeguard spatiotemporal organization was a fundamental question towards understanding the process of protein degradation and its functions in diverse biological processes. In this review we will dismantle how HECT E3 enzymes regulate the trafficking of many receptors, channels and transporters as well as how HECT enzymes negatively regulate each other. There is accumulating evidence that suggests an undeniable role of HECT enzymes in regulating mediators of the Wnt signal-transduction cascade. By contrast, little is known about the crosstalk of HECT enzymes with ATM and TRAIL in prostate cancer, but several hints have emerged. This review provides a broader snapshot for studying multiple pathways in parallel, rather than as separate entities.

PDGF: the nuts and bolts of signalling toolbox.

PDGF is a growth factor and is extensively involved in multi-dimensional cellular dynamics. It switches on a plethora of molecules other than its classical pathway. It is engaged in various transitions of development; however, if the unleashed potentials lead astray, it brings forth tumourigenesis. Conventionally, it has been assumed that the components of this signalling pathway show fidelity and act with a high degree of autonomy. However, as illustrated by the PDGF signal transduction, reinterpretation of recent data suggests that machinery is often shared between multiple pathways, and other components crosstalk to each other through multiple mechanisms. It is important to note that metastatic cascade is an intricate process that we have only begun to understand in recent years. Many of the early steps of this PDGF cascade are not readily targetable in the clinic. In this review, we will unravel the paradoxes with reference to mitrons and cellular plasticity and discuss how disruption of signalling cascade triggers cellular proliferation phase transition and metastasis. We will also focus on the therapeutic interventions to counteract resultant molecular disorders.