Background: Flow-dependent concentration polarization of native LDL is important in the localization of atherogenesis. However, ox-LDL plays a more important role than n-LDL in atherogenesis by inducing cell proliferation and apoptosis. We hypothesized that concentration polarization of ox-LDL may adversely affect vascular beds due to its toxicity to endothelial cell (EC) lining. Methods: Using a parallel-plate flow chamber technique, we studied water filtration rate and wall concentration of ox-LDLs EC monolayers cultured on permeable or non-permeable membranes. ECs cultured on permeable and non-permeable membranes were examined in terms of cell viability, ox-LDL uptake, LOX-1 expression and cell apoptosis (Cytochrome c and Bcl-2 expression). We observed that the wall concentration of ox-LDL was about 16% higher in the permeable group than in the permeable group (P<0.05). Cell proliferation (MTT assay) increased in response to low concentration of ox-LDL (1-5 μg/ml), and fell drastically in response to higher concentration; all these changes were more pronounced in the permeable group than in the non-permeable group. The uptake of ox-LDL and LOX-1 expression by ECs were also significantly higher in the permeable group than in the non-permeable group of cultured cells. Conclusions: These observations suggest that concentration polarization of ox-LDL occurs in an artery that is permeable to water, and ox-LDL concentration polarization can enhance ox-LDL accumulation into the arterial wall and accelerate EC proliferation at low concentrations and apoptosis at high concentrations, possibly via LOX-1 expression.

Emerging evidence indicates that micronutrient deficiency could play a significant role in the pathogenesis and progression of many chronic diseases including diabetes mellitus, hypertension, obesity, dyslipidemia, hyperuricemia, kidney disease, cancer, anemia and other cardio-metabolic and neurodegenerative diseases through the induction of Insulin resistance (IR). However, there are still gaps in our scientific knowledge regarding the links between micronutrient deficiencies, IR, and cardio metabolic disorders. This review provides current information on recent advances and a global perspective regarding the relationship between micronutrient deficiency, IR, and cardio metabolic disorders. Empirical evidence indicates that deficiencies in either micronutrients associated with insulin activity (such as Chromium, manganese, magnesium, and iron) or antioxidant enzyme cofactors (such as vitamin A, copper, zinc, and manganese) could impact several physiological processes leading to a cascade of metabolic and biochemical derangements such as B-cell apoptosis, loss of islet cell mass, defective tyrosine kinase activity, oxidative stress, pancreatic β-cell dysfunction, reduction in lean body mass, defective insulin signaling mechanism, elevated protein kinase C activity, and excess intracellular calcium. Collaboratively, these states of metabolic malfunctioning are associated with IR, which triggers the onset of many cardio metabolic diseases. Undoubtedly, the prevention of micronutrient deficiency may indeed ameliorate the incidence of IR and cardio-metabolic disorders in those at risk and in the general population.

Owing to the ever westernizing lifestyles in developing countries like India, the escalation of oral cancer patients are in need of urgent plan of action. With tobacco being the commonest cause for causation of oral cancer, Global Adult Tobacco Survey, 2016-17 revealed that almost 28% of whole population of India is consuming tobacco in either smoking or smokeless form. With these increasing numbers, the expected death toll to be expected to touch 1-2 million mark by the year 2035 [1]. Although, the current Onco-medicine fraternity excels in rendering care to oral cancer patients in the form of surgeries, chemotherapy and radiation-therapy. Often, these treatment modalities impart some unwanted adverse effects like, docetaxel (DCT) is known for its hepatotoxicity [2,3] whereas, one of the commonly used cisplatin (CIS) presents with nephrotoxicity, neurotoxicity, bone marrow suppression and vomiting [4,5]. Literature suggests of many non conventional medicaments being tested in past for their anti onco-genic effect, where few being effective and others being questionable ones. Chlorhexidine being one among them showing some how promising anti onco-genic activity with feeble amount of studies being conducted in past. Chlorhexidine, one of the most commonly prescribed mouthrinse in the field of dentistry, with varying concentrations of 0.12% and 0.2% concentrations. Although, apart from being broad spectrum antibiotic, its capability to dismantle the protein – protein bond between anti – apoptotic Bcl-2 family protein Bcl-xL and its pro – apoptotic binding partners [6]. The current study was conducted on three cell lines of squamous cell carcinoma (SCC-4, SCC-9, SCC -15) and two pharynx carcinoma cell lines (FaDu and Detroit 562). The compounds induced apoptosis through mitochondria dependent apoptotic pathway in oral tumour cell lines. Another study conducted to assess the similar anti – oncogenic activites of chlorhexidine mouthrinse along with cranberry [7]. It was evident from results that, with increasing concentrations of chlorhexidine mouthrinse, there was increase in mean percent growth inhibition. The authors concluded saying, chlorhexidine has showed both anti cancerous as well as anti bacterial activity required to tackle common oral infections, part of common anti cancer therapy. Fernando Martínez-Pérez et al (2019) conducted study, where antitumor activity of Lipophilic Bismuth Nanoparticles (BisBAL NPs) and chlorhexidine on human squamous cell carcinoma was assessed using energy dispersive X – ray spectroscopy in conjunction with scanning electron microscopy (EDS-SEM). Study revealed, BisBAL NPs and chlorhexidine both showed cell growth inhibition on both cancer cell line (CAL-27) and human gingival fibroblasts (HGFs). Although, chlorhexidine showed non specific cytotoxicity for both tumoral and non tumoral control cells. The suggestive mechanism of action might be loss of cell membrane integrity [8]. Although Eliot MN (2013) conducted study, to assess the risk of head and neck squamous cell carcinoma secondary to use of alcohol containing and non alcoholic mouthwashes including chlorhexidine. The study was concluded with an assumption based on chlorhexidine mouthwash alters the oral flora [9], thus resulting in increasing risk exponentially through diverse change in oral bacteria and altered immune response with contribution towards genesis or promotion of cancer [10]. On the contrary, alcohol consumption and smoking are predisposing factors towards upper digestive tract cancer. The main causative factor being the first metabolite of alcohol, acetaldehyde. And much higher levels are derived from oral bacteria and thus, same can be altered in favour through usage of chlorhexidine mouthwash, to avoid excessive production of acetaldehyde intra orally. In conclusion, chlorhexidine mouthwash has been into dental practice since long and the role it plays in either ways has to be assessed by a multi dimensional study with cell lines including that of control to derive better compared conclusions.

Sepsis refers to a generalized inflammatory response of the organism to an infection or to bacterial products in circulation, rather than the development of an infection per se. Despite recent advances in clinical practice and overall medical care, sepsis remains a great health care problem and is still the most common cause of death in critically ill patients with infection. We suppose that during the course of sepsis the expression of TRAIL in different organs correlates with acute mortality and further development of multiple organ dysfunction syndrome (MODS). It is expected that dendritic cells (DCs) might become targets for apoptotic processes in a result of elevated TRAIL expression. This hypothesis is a bias for detailed investigations for in vivo studies in animal models and for in vitro studies of septic patients.

In the actual medical therapy of BPH, we can see: antibiotics, alpha blockers, 5-ARI, fitotherapeutics/natural products (Serenoa repens) with different which display clinical activities and other molecules such as FANS (local or systemic dosage forms) cortisones and others. Relationship between immune systems and chronic prostatitis are strictly involved in BPH progression. A vicious cycle that involve chronic flogosis, tissue remodeling, grow factors, inhibition of apoptosis, and other phenomena. Observing BPH pathogenesis under an immunologic point of view make possible to search new pharmacological strategies, to improve actual therapy. The aim of this work is to observe some relevant literature in our opinion related the management of BHP and its progression under a pharmaceutical and immunological point of view. A deep knowledge in the pharmaceutical properties of some molecules (antimicrobials, anti-phlogosis agents, Anti-androgenic agents, alpha blockers, 5-ARI and other treatments, techniques, interventions or instruments) can help the physicians to pick the right choice.

The Positive Regulatory Domain (PRDM) protein family gene is involved in a spectrum variety of biological processes, including proliferation, differentiation and apoptosis: its member seem to be transcriptional regulators highly cell type and tissue peculiar, towards histones modifications or recruitment of specific interaction patters to modify the expression of target genes. In this study we analyzed the expression profile of different member of PRDM gene family focusing our attention on the role of PRDM2, PRDM4 and PRDM10 genes in mouse C2C12 cell line, during the differentiation of myoblasts into myotubes and speculate about the role of the protein Retinoblastoma protein-interacting zinc finger protein 1-RIZ1, coded by PRDM2 gene, as a regulator of the proliferation/differentiation switch. Results showed a reduction of PRDM2, PRDM4 and PRDM10 expression level during the commitment of the differentiation of myoblasts into myotubes. The RIZ1 silencing stimulated myoblasts differentiation, similar to the effect of serum deprivation on these cells, associated with an increase of Myogenin expression level, which is considered to be involved in the differentiation of myoblasts into multinucleated myotubes. As demonstrated by chromatin immunoprecipitation experiments, RIZ1 is associated with Myogenin promoter in proliferation condition and after 24h from differentiation induction, negatively controlling therefore Myogenin expression. Moreover RIZ1 silencing induced a reduction in PRDM4 and PRDM10 expression levels leaving us to speculate that the PRDM genes have a redundant role and they are hierarchically organized.

Previous clinical, observation and epidemiologic studies have demonstrated strong association between serum uric acid (SUA) and cardiovascular disease (hypertension, heart failure, and asymptomatic atherosclerosis), metabolic states (abdominal obesity, diabetes mellitus, metabolic syndrome, insulin resistance) and kidney disease. There is a large body of evidence regarding the role of SUA as predictor of CV events and CV mortality in general population and individuals with established CV disease and metabolic diseases. However, SUA may exhibit protective effects on endothelium and vasculature as well as attenuate endogenous repair system through mobbing and differentiation of cell precursors. Although SUA lowering drugs are widely used in patients with symptomatic hyperuricemia and gout beyond their etiologies, there is no agreement of SUA below target level 6.0 mg/dL in asymptomatic individuals with kidney injury and CV disease and data of ones are sufficiently limited. The short communication is depicted on the controversial role of SUA as primary cell toxicity agent and secondary cell protector against hypoxia, ischemia and apoptosis

Although exercise has been proposed to be beneficial to type 2 diabetes, its effects on β-cell function and mass remain unclear. In the present study, the effects of long-term swimming training on the function and mass of β-cells in diabetic OLETF rats were examined. At 44 weeks of age after developing diabetes, the OLETF rats were divided into two groups: a control group and an exercise group. The exercise group had a daily swimming for 12 weeks. While not found with the control rats, in the obese OLETF rats, the exercise reduced the weight gain which was associated with improved glucose tolerance and elevated circulating insulin levels as determined by the oral glucose tolerance test and insulin ELISA. The exercise improved plasma total cholesterol and triglyceride levels, and also significantly increased the islet β-cell mass and pancreatic insulin content associated with decreased β-cell apoptosis and elevated activation of the serine/threonine kinase, Akt. The present studies suggest that exercise improves diabetes symptoms via enhancement of the β-cell mass and function through decreasing glucolipotoxicity and reducing β-cell apoptosis by activating Akt in obese OLETF rats.

Delayed cerebral ischemia (DCI) is one of the main complications of spontaneous subarachnoid haemorrhage and one of its causes is the cortical spreading depolarizations (CSDs). Cortical spreading depolarizations are waves of neuronal and glial depolarizations in which there is loss of neuronal ionic homeostasis with potassium efflux and sodium and calcium influx. In damaged brain areas and brain areas at risk, such as those adjacent to subarachnoid haemorrhage (SAH), CSDs induce microvascular vasoconstriction and, therefore, hypoperfusion and spread of ischemia. Several studies have been devoted to minimize secondary injuries that occur hours to days after an acute insult. Ketamine, a drug until recently contraindicated in the neurosurgical population for potentially causing intracranial hypertension, has re-emerged as a potential neuroprotective agent due to its pharmacodynamic effects at the cellular level. These effects include anti-inflammatory mechanisms, and those of microthrombosis and cell apoptosis controls, and of modulation of brain excitotoxicity and CSDs. A literature review was performed at PubMed covering the period from 2002 to 2019. Retrospective studies confirmed the effects of ketamine on the control of CSDs and, consequently, of DCI in patients with SAH, but did not show improvement in clinical outcome. The influence of ketamine on the occurrence/development of DCI needs to be further confirmed in prospective randomized studies

The SARS-Cov-2 virus was firstly identified in Wuhan, China and caused catastrophic destruction all over the world. COVID-19 virus primarily effects lungs of its hosts and impairs it in number of ways. It can also damage multiple organs like Heart, kidney, endocrine glands, skin, brain and several others. Kidneys are also damaged to a great extent. In Heart it can cause acute coronary syndrome, Heart failure, Myocardial infarction. SARS-CoV-2 effect brain especially psychologically. It also causes serious lymphocyte apoptosis. It also neutralizes human spleen and lymph nodes. SARS-CoC-2 can be harmful for those having already liver diseases. Similarly, SARS-CoV-2 has a direct impact on endocrine glands. It is responsible for the various injurious changes in hormones, causes various diseases like acute pancreatitis, decrease in GH, hypoparathyroidism etc. and lead to cause tissues damage in glands. It also some minor effects on nose, and respiratory pathways. It also has some minor effects on eyes and ears whereas it causes several devastations in GIT.

For a long time there was no explanation of a study which had revealed that people with schizoaffective disorders and in particular suicidal attempts rarely get cancer. But now, we can assume that there are diseases that are “mirrored” because they occur with reverse/feedback pathophysiological mechanisms so that they are, in fact, antagonists.

Boron and their derived molecules have prevention or treatment potential against prostate cancer. In this study, we aim to investigate the effects of Boric acid (BA) and Disodium Pentaborate Dechydrate (DPD) in metastatic prostate cancer cells such as DU-145 which is brain metastatic prostate cancer, and PC3 which is bone metastatic prostate cancer.Metastatic human prostate cancer cell lines, PC-3 and DU-145, were used to show whether inhibition effects of BA and DPD on prostate cancer cells in this study. BA and DPD were applied for 24 hours to the cells. Cell viability determination was performed using WST-1 assay. Apoptotic cell death was evaluated with Annexin-V/PI flow cytometric analysis and caspase-3 expression immunohistochemically. A wound healing assay was also used to measure cancer cell migration after exposure to BA and DPD.Applying BA and DPD made inhibition of cell proliferation in both BA (1 mM) and DPD (7 mM) at 24 h. The results of Annexin-V/PI showed that DPD induced higher levels of apoptosis than BA in both prostate cancer cells. Caspase-3 expressions were also higher than BA with DPD in both metastatic prostate cancer cells. We evaluated cell migration using a wound healing assay and the result showed that cell migration was inhibited with BA and DPD in both cells. Both BA and DPD inhibited the cell viability of metastatic prostate cancer cells. Apoptotic cell death with applying DPP had a higher rate than BA treatment. Moreover, BA and DPD inhibited cell migration in both cells when we compared them with control. This study’s results showed that BA and DPD of boron derivates significantly induced cells to apoptosis and the migration was inhibited by the derived form of boron in metastatic prostate cancer cells.

The pathogenesis of an ovarian disease is connected with PTN and its receptor protein tyrosine phosphatase receptor Z1 (PTPRZ1). Paclitaxel is the first-line drug for the therapy of ovarian cancer. With the increment of paclitaxel chemotherapy, paclitaxel obstruction happens in the late phase of therapy frequently. By treating A2780 and SKOV-3 cells with PTN, we found the development of the two cell lines was enhanced. Different concentrations of PTN were added to A2780 and SKOV-3 cells treated with paclitaxel and the results of MTT showed that the inhibitory effect of paclitaxel on these two cell lines was weakened. The results of apoptosis assays showed that PTN could slow down the rate of apoptosis and its concentration dependence in both cell lines. To further investigate the impact of PTN on the paclitaxel responsiveness of ovarian malignant growth cells, A2780 and SKOV-3 cells were transfected with sh-PTN-1, sh-PTN-2 and sh-NC plasmids. The results of PCR and Western Blot showed that both RNA-interfering plasmids could inhibit PTN in A2780 and SKOV-3 cells. The results of MTT showed that the inhibitory effect of paclitaxel on cells transfected with sh-PTN-1 expanded compared with the benchmark group. Apoptosis assays showed that the complete apoptosis pace of A2780 and SKOV-3 cells with sh-PTN-1 plasmid induced by paclitaxel was accelerated obviously compared with the benchmark group. To summarize, the results suggested that PTN could enhance the resistance to paclitaxel in ovarian cancer cells, which provides a groundwork for studying on drug resistance of cancer cells to paclitaxel and a new perspective for ovarian cancer therapy.

Genistein is an isoflavone glycoside that provides a variety of health advantages. The possibility of cancer chemopreventive drugs derived from natural sources, such as polyphenols, may constitute a novel, cost-effective strategy to reduce the rising burden of cancer throughout the world. A soy-rich diet was linked to cancer prevention in several epidemiological studies, which was explained by the presence of the phenolic component genistein in soy-based foods. Inhibiting metastasis and changing apoptosis, the cell cycle, and angiogenesis are the key ways that genistin fights various cancers. It acts as a chemotherapeutic agent against different types of cancer, mainly by altering apoptosis, the cell cycle, and angiogenesis and inhibiting metastasis. This study critically evaluates the literature that is currently available on the therapeutic benefits of genistin for various cancers.

Background and aim: Preclinical in vitro and in vivo experiments suggest that radiation-induced tumour cell death can be enhanced 10- to 40-fold when combined with focused-ultrasound (FUS)-stimulated microbubbles (MB). The acoustic exposure of MB in the tumour volume causes vasculature perturbation, activation of the acid sphingomyelinase (ASMase) ceramide pathway, and resultant endothelial cell apoptosis. When the tumour is subsequently treated with radiation, there is increased endothelial cell death and anoxic tumour killing. Here we describe a first-in-human experience treating patients with magnetic resonance (MR)-guided FUS-stimulated MB (MRgFUS+MB) radiation enhancement.Case presentation: A head and neck cancer patient with recurrent disease underwent radiotherapy for 5 separate sites of locoregional disease followed by systemic therapy. The first consisted of a course of 45 Gy in 5 fractions alone, the second of 30 Gy in 5 fractions with hyperthermia, and the three others of 20-30 Gy in 5 fractions along with MRgFUS+MB treatment. The treatment methodology used an MR-coupled FUS-device operating at 500 KHz and 540 kPa peak negative pressure with an insonification time of 750 ms spread over 5 minutes to stimulate intravenously administered MB within tumour target. All sites treated with stimulated MB had a complete radiological response, and subsequently, the patient’s other cutaneous metastatic disease disappeared. The patient has been under surveillance for over two years without active treatment or disease progression.Discussion: MRgFUS+MB was well-tolerated with no reported treatment-related adverse events, which can be attributed to the capability of FUS to selectively stimulate MB within the tumour volume while sparing the surrounding normal tissue. Sustained local control at all target sites aligns with earlier preclinical findings suggesting the radiation enhancement potential of FUS+MB.Conclusion: MRgFUS+MB represents a novel and promising therapy for enhancing radiation efficacy and improving therapeutic index with potential improvements in disease control.

Alzheimer’s disease, a major healthcare concern, lacks an effective pharmacological therapy to change its irreversible progression. In this work, we present Klotho, a protein associated with aging that is involved in the regulation of numerous physiological processes and is a serious candidate to be a pharmacological target to act on. Klotho’s mRNA has been found in neurons of a variety of brain regions (cortex, hippocampus). The best studied and prominent function of Klotho is as the co-receptor of fibroblast growth factor 23 (FGF23), through which Klotho controls renal phosphate excretion and vitamin D metabolism. Reduced serum levels of Klotho in mice have been associated with a shorter life expectancy and with numerous pathological conditions such as renal disease, vascular calcification, neurodegeneration, and others. Moreover, overexpression of Klotho leads to opposite effects resulting in increased survival rates. In this review we address different signaling pathways in which Klotho is involved in one way or another, focusing on those pathways that could serve as pharmacological targets to modify the evolution of Alzheimer’s disease. We describe how Klotho inhibits signaling cascades involved in cellular senescence, fibrosis, inflammation, and apoptosis all of which are mediated by tumor growth factor β (TGF- β), nuclear factor kappa K (NF- κ B), insulin-like growth factor 1 (IGF-1) or Wnt. We also highlight how Klotho is able to activate anti-inflammatory and antioxidant signaling pathways.  Although there are no drugs that act specifically on Klotho, compounds currently on the market such as hormone-based drugs, pravastatin, losartan, fosinopril, and rapamycin have been shown to increase the expression of this protein and are also discussed.