Network Meta-analysis of Randomised Controlled Trials Comparing the Outcomes of Different Endovascular Revascularisation Treatments for Infra-inguinal Peripheral Arterial Disease Causing Chronic Limb Threatening Ischaemia.

OBJECTIVE: The aim of this study was to compare the efficacy of different endovascular revascularisation procedures for treating chronic limb threatening ischaemia (CLTI) using network meta-analysis (NMA). DATA SOURCES: The databases PubMed and Cochrane Central Register for Controlled Trials were searched on 14 March 2023. REVIEW METHODS: A NMA of randomised controlled trials (RCTs) reporting the efficacy of different endovascular revascularisation techniques for treating CLTI was performed according to PRISMA guidelines. The primary and secondary outcomes were major amputation and death, respectively. Random effects models were developed and the results were presented using surface under the cumulative ranking curve plots and forest plots. A p value of ≤ .050 was considered statistically significant. The Cochrane collaborative tool was used to assess risk of bias. RESULTS: A total of 2 655 participants of whom 94.8% had CLTI were included. Eleven trials compared plain balloon angioplasty (PBA) vs. drug coated balloon (DCB) angioplasty (n = 1 771), five trials compared bare metal stent (BMS) vs. drug coated stent (DCS) (n = 466), three trials compared atherectomy vs. DCB (n = 194), two trials compared PBA vs. BMS (n = 70), one trial compared PBA vs. atherectomy (n = 50), and one trial compared BMS vs. DCB (n = 104). None of the revascularisation strategies significantly reduced the risk of major amputation or death compared with PBA. Using the network estimates, GRADE certainty of evidence for improvement in major amputation outcomes for DCB was moderate, for atherectomy and BMS was low, and for DCS was very low compared with PBA. Risk of bias was low in 16 trials, of some concerns in six trials, and high in one trial, respectively. CONCLUSION: There is no current evidence from RCTs to reliably conclude that BMS, DCB, DCS, or atherectomy are superior to PBA in preventing major amputation and death in patients with CLTI. Larger comparative RCTs are needed to identify the best endovascular revascularisation strategy.

Comparative efficacy of growth factor therapy in healing diabetes-related foot ulcers: A network meta-analysis of randomized controlled trials.

INTRODUCTION: This study examined the relative efficacy of growth factor therapies in healing diabetes-related foot ulcers (DFU). METHODS: PubMed and Cochrane databases were searched for randomized controlled trials testing growth factor therapies for treating DFU. The primary outcome was complete wound closure. Results were reported as relative risk (RR) ± 95% credible intervals (CrI). The risk of bias was assessed using Cochrane's RoB-2 tool. RESULTS: A total of 31 RCTs involving 2174 participants were included. Only 13 of the trials (n = 924) reported on the aetiology of the ulcers (85.4% neuropathic and 14.6% ischaemic). Epidermal growth factor (RR 3.83; 95% CrI 1.81, 9.10), plasma-rich protein (PRP) (RR 3.36; 95% CrI 1.66, 8.03) and platelet-derived growth factor (PDGF) (RR 2.47; 95% CrI 1.23, 5.17) significantly improved the likelihood of complete ulcer healing compared to control. Sub-analyses suggested that PRP (3 trials - RR 9.69; 95% CrI 1.37, 103.37) and PDGF (6 trials - RR 2.22; 95% CrI 1.12, 5.19) significantly improved the likelihood of wound closure amongst trial mainly recruiting participants with neuropathic ulcers. Eleven trials had a low risk of bias, 9 had some concerns and 11 had a high risk of bias. Sub-analysis of trials with a low risk of bias suggested that none of the growth factors significantly improved ulcer healing compared with control. DISCUSSION: This network meta-analysis found low-quality evidence that Epidermal growth factor, PRP and PDGF therapy improved DFU healing likelihood compared with control. Larger well-designed trials are needed.

Current trends and future prospective in nanoremediation of heavy metals contaminated soils: A way forward towards sustainable agriculture.

Heavy metals (HMs) contamination in agricultural soils is a major concern for global food safety and human health. Although, various in-situ and ex-situ remediation methods have been used for the treatment of HMs contaminated soils, however, they also have many drawbacks viz., capital investment, toxicity, and environmental health hazards. Consequently, there is an urgent need to develop a novel method to ameliorate the toxicity of HMs in agricultural soils. In recent years, nanoparticles (NPs) have gained significant attention due to their potential applications in the environment and agriculture fields. Nanoremediation employs NPs that effectively reduce the contents of toxic HMs in the soil-plant system. Several studies have reported that the application of NPs in HMs-polluted soils, which reduced plant-available HMs concentration soils. However, the long-term efficiency of NPs immobilization is still unclear. Here, we provide details about the toxicity of HMs to environmental systems and potential applications NPs to alleviate the accumulation of HMs in agricultural soils. Finally, we present the mechanistic route of HMs-toxicity alleviation in plants by NPs application as well as their long-term efficiency and future prospects.

Evidence for the Desmosomal Cadherin Desmoglein-3 in Regulating YAP and Phospho-YAP in Keratinocyte Responses to Mechanical Forces.

Desmoglein 3 (Dsg3) plays a crucial role in cell-cell adhesion and tissue integrity. Increasing evidence suggests that Dsg3 acts as a regulator of cellular mechanotransduction, but little is known about its direct role in mechanical force transmission. The present study investigated the impact of cyclic strain and substrate stiffness on Dsg3 expression and its role in mechanotransduction in keratinocytes. A direct comparison was made with E-cadherin, a well-characterized mechanosensor. Exposure of oral and skin keratinocytes to equiaxial cyclic strain promoted changes in the expression and localization of junction assembly proteins. The knockdown of Dsg3 by siRNA blocked strain-induced junctional remodeling of E-cadherin and Myosin IIa. Importantly, the study demonstrated that Dsg3 regulates the expression and localization of yes-associated protein (YAP), a mechanosensory, and an effector of the Hippo pathway. Furthermore, we showed that Dsg3 formed a complex with phospho-YAP and sequestered it to the plasma membrane, while Dsg3 depletion had an impact on both YAP and phospho-YAP in their response to mechanical forces, increasing the sensitivity of keratinocytes to the strain or substrate rigidity-induced nuclear relocation of YAP and phospho-YAP. Plakophilin 1 (PKP1) seemed to be crucial in recruiting the complex containing Dsg3/phospho-YAP to the cell surface since its silencing affected Dsg3 junctional assembly with concomitant loss of phospho-YAP at the cell periphery. Finally, we demonstrated that this Dsg3/YAP pathway has an influence on the expression of YAP1 target genes and cell proliferation. Together, these findings provide evidence of a novel role for Dsg3 in keratinocyte mechanotransduction.

AST to ALT Ratio is elevated in disseminated histoplasmosis as compared to localized pulmonary disease and other endemic mycoses.

Severe pulmonary or disseminated histoplasmosis often necessitates presumptive antifungal treatment while awaiting definitive diagnosis. Histoplasma antigen assays have improved sensitivity but results may lag up to 7 days. In order to increase diagnostic certainty, "soft clues" may be looked for in laboratory and radiologic data, such as elevated alkaline phosphatase or ferritin levels and findings of mediastinal adenopathy or hepatosplenomegaly. To determine if elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio is specific to histoplasmosis or a non-specific marker for disseminated fungal infection or sepsis in general, we retrospectively examined records of all patients diagnosed with an endemic fungal infection (EFI) at Rush University Medical Center from January of 1997 to October of 2012, and a cohort of septic patients with elevated liver enzymes. We identified 90 cases of EFIs during the study period that met all inclusion criteria (Histoplasma 21, Blastomyces 56, Coccidioides 12, Paracoccidioides 1). We also evaluated 10 control patients with bacterial sepsis. The mean ratio of AST to ALT in patients with disseminated histoplasmosis was 2.69 (95% CI:1.22, 4.16) while for other EFIs, the mean ratio ranged from 0.38 to 1.14 with disseminated coccidioidomycosis and blastomycosis respectively (P < 0.0001). The ratio in patients with bacterial sepsis was 0.84. We propose the use of the AST/ALT ratio as a clinical "soft clue" suggestive of disseminated histoplasmosis in the appropriate host, and to possibly distinguish cross reactivity of the Histoplasma antigen assay with other EFIs.

Comparative Transcriptome Analysis Identifies Desmoglein-3 as a Potential Oncogene in Oral Cancer Cells.

The role of desmoglein-3 (DSG3) in oncogenesis is unclear. This study aimed to uncover molecular mechanisms through comparative transcriptome analysis in oral cancer cells, defining potential key genes and associated biological processes related to DSG3 expression. Four mRNA libraries of oral squamous carcinoma H413 cell lines were sequenced, and 599 candidate genes exhibited differential expression between DSG3-overexpressing and matched control lines, with 12 genes highly significantly differentially expressed, including 9 upregulated and 3 downregulated. Genes with known implications in cancer, such as MMP-13, KRT84, OLFM4, GJA1, AMOT and ADAMTS1, were strongly linked to DSG3 overexpression. Gene ontology analysis indicated that the DSG3-associated candidate gene products participate in crucial cellular processes such as junction assembly, focal adhesion, extracellular matrix formation, intermediate filament organisation and keratinocyte differentiation. Validation of RNA-Seq was performed through RT-qPCR, Western blotting and immunofluorescence analyses. Furthermore, using transmission electron microscopy, we meticulously examined desmosome morphology and revealed a slightly immature desmosome structure in DSG3-overexpressing cells compared to controls. No changes in desmosome frequency and diameter were observed between the two conditions. This study underscores intricate and multifaceted alterations associated with DSG3 in oral squamous carcinoma cells, implying a potential oncogenic role of this gene in biological processes that enable cell communication, motility and survival.

Protein Kinases and their Inhibitors Implications in Modulating Disease Progression.

Protein phosphorylation plays an important role in cellular pathways, including cell cycle regulation, metabolism, differentiation and survival. The protein kinase superfamily network consists of 518 members involved in intrinsic or extrinsic interaction processes. Protein kinases are divided into two categories based on their ability to phosphorylate tyrosine, serine, and threonine residues. The complexity of the system implies its vulnerability. Any changes in the pathways of protein kinases may be implicated in pathological processes. Therefore, they are regarded as having an important role in human diseases and represent prospective therapeutic targets. This article provides a review of the protein kinase inhibitors approved by the FDA. Finally, we summarize the mechanism of action of protein kinases, including their role in the development and progression of protein kinase-related roles in various pathological conditions and the future therapeutic potential of protein kinase inhibitors, along with links to protein kinase databases. Further clinical studies aimed at examining the sequence of protein kinase inhibitor availability would better utilize current protein kinase inhibitors in diseases. Additionally, this review may help researchers and biochemists find new potent and selective protein kinase inhibitors and provide more indications for using existing drugs.

Analyzing the Challenges, Consequences, and Possible Treatments for Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a highly widespread disorder caused by a disturbed endocrine system. The Rotterdam criteria have classified 4 phenotypes of PCOS. This syndrome has multifactorial pathophysiology triggered by a disturbed neuroendocrine system, which further produces abnormal levels of luteinizing hormone, follicle-stimulating hormone, androgen, estrogen, and progesterone, leading towards the risk of metabolic and reproductive diseases. PCOS is associated with an increased risk of developing health problems like hyperinsulinemia, diabetes mellitus, hypertension, cardiovascular disorders, dyslipidaemia, endometrial hyperplasia, anxiety and depression. These days, PCOS has become a scientific issue due to complex aetiology with multi- complex physiology. Due to the unavailability of specific medicines, there is no cure for PCOS; however, certain symptoms could be treated. The scientific community is actively looking for various treatment options too. In this context, the current review summarizes the challenges, consequences and various treatment options for PCOS. Various literature reports provide evidence that PCOS can be identified in early infancy, adolescents and women at the menopausal stage. Most commonly, PCOS is caused by multifactorial agents, including genetics and negative lifestyle. Metabolic consequences from obesity, insulin resistance, and vascular disorder have increased the rate of PCOS. This study also highlights psychological morbidity in PCOS women that have an adverse effect on health-related quality of life (HRQoL). PCOS symptoms can be treated using different strategies, including oral contraceptive drugs, surgical treatment (laparoscopic ovarian drilling (LOD), assisted reproductive techniques (ART), and Chinese acupuncture treatment.

Desmoglein-3 induces YAP phosphorylation and inactivation during collective migration of oral carcinoma cells.

Alterations of the Hippo-YAP pathway are potential targets for oral squamous cell carcinoma (OSCC) therapy, but heterogeneity in this pathway could be responsible for therapeutic resistance. We analysed the Hippo-YAP signatures in a cohort of characterised keratinocyte cell lines derived from the mouth floor and buccal mucosa from different stages of OSCC tumour progression and focused on the specific role of YAP on invasive and metastatic potential. We confirmed heterogeneity in the Hippo-YAP pathway in OSCC lines, including overexpression of YAP1, WWTR1 (often referred to as TAZ) and the major Hippo signalling components, as well as the variations in the genes encoding the intercellular anchoring junctional proteins, which could potentially regulate the Hippo pathway. Specifically, desmoglein-3 (DSG3) exhibited a unique and mutually exclusive regulation of YAP via YAP phosphorylation during the collective migration of OSCC cells. Mechanistically, such regulation was associated with inhibition of phosphorylation of epidermal growth factor receptor (EGFR) (S695/Y1086) and its downstream effectors heat shock protein beta-1 (Hsp27) (S78/S82) and transcription factor AP-1 (c-Jun) (S63), leading to YAP phosphorylation coupled with its cytoplasmic translocation and inactivation. Additionally, OSCC lines displayed distinct phenotypes of YAP dependency or a mixed YAP and TAZ dependency for cell migration and present distinct patterns in YAP abundance and activity, with the latter being associated with YAP nuclear localisation. In conclusion, this study provides evidence for a newly identified paradigm in the Hippo-YAP pathway and suggests a new regulation mechanism involved in the control of collective migration in OSCC cells.

The Regulation of the Hippo Pathway by Intercellular Junction Proteins.

The Hippo pathway is an evolutionarily conserved pathway that serves to promote cell death and differentiation while inhibiting cellular proliferation across species. The downstream effectors of this pathway, yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ), are considered vital in promoting the output of the Hippo pathway, with activation of upstream kinases negatively regulating YAP/TAZ activity. The upstream regulation of the Hippo pathway is not entirely understood on a molecular level. However, several studies have shown that numerous cellular and non-cellular mechanisms such as cell polarity, contact inhibition, soluble factors, mechanical forces, and metabolism can convey external stimuli to the intracellular kinase cascade, promoting the activation of key components of the Hippo pathway and therefore regulating the subcellular localisation and protein activity of YAP/TAZ. This review will summarise what we have learnt about the role of intercellular junction-associated proteins in the activation of this pathway, including adherens junctions and tight junctions, and in particular our latest findings about the desmosomal components, including desmoglein-3 (DSG3), in the regulation of YAP signalling, phosphorylation, and subcellular translocation.

YAP Inhibition by Verteporfin Causes Downregulation of Desmosomal Genes and Proteins Leading to the Disintegration of Intercellular Junctions.

The Hippo-YAP pathway serves as a central signalling hub in epithelial tissue generation and homeostasis. Yes-associated protein (YAP) is an essential downstream transcription cofactor of this pathway, with its activity being negatively regulated by Hippo kinase-mediated phosphorylation, leading to its cytoplasmic translocation or degradation. Our recent study showed phospho-YAP complexes with Desmoglein-3 (Dsg3), the desmosomal cadherin known to be required for junction assembly and cell-cell adhesion. In this study, we show that YAP inhibition by Verteporfin (VP) caused a significant downregulation of desmosomal genes and a remarkable reduction in desmosomal proteins, including the Dsg3/phospho-YAP complex, resulting in attenuation of cell cohesion. We also found the desmosomal genes, along with E-cadherin, were the YAP-TEAD transcriptional targets and Dsg3 regulated key Hippo components, including WWTR1/TAZ, LATS2 and the key desmosomal molecules. Furthermore, Dsg3 and phospho-YAP exhibited coordinated regulation in response to varied cell densities and culture durations. Overexpression of Dsg3 could compensate for VP mediated loss of adhesion components and proper architecture of cell junctions. Thus, our findings suggest that Dsg3 plays a crucial role in the Hippo network and regulates junction configuration via complexing with phospho-YAP.

Exploring Liposomes for Lung Cancer Therapy.

Cancer is referred to as a pleiotropic disease-causing approximately 9.6 million deaths in 2018. Among all cancers, lung cancer was the leading cause of death in 2017, and 12% of fatalities were alone due to lung cancer. The associated risk factors in lung cancer include smoking (80-85%), chronic inflammation in the lungs, COPD, pulmonary fibrosis, environmental and occupational exposure to nickel, arsenic, chromates, etc. Early diagnosed patients' treatment plan includes chemotherapy, immunotherapy, radiotherapy, surgery, and tumor ablation. Many sorts of drug delivery carriers have been used in the past, usually in targeted chemotherapy. Liposomes are spherical shape vesicles containing a lipid bilayer and aqueous core, with potency to encapsulate both hydrophobic and hydrophilic drugs with minimal toxicity. These vesicles have a particle size of 0.02-1000 µm allowing selective passive targeting to the tumor's deeper tissues. Current publications on liposomes highlight their acceptance and best choice among all systems to deliver synthetic and herbal drugs to the lungs. This review focuses on many aspects, which include an in-depth analysis of potential anticancer drugs that have utilized the advantages of liposomes for effective lung carcinomatherapy and devices used to deliver the active agents to the pulmonary tissues. Investigations on ongoing, approved, and failed clinical trials and patents on products related to lung cancer have been highlighted to provide a critical review on the subject.

Armamentarium in Drug Delivery for Colorectal Cancer.

Colorectal cancer (CRC) is the second most common cause of cancer related deaths in the United States. However, more than half of all incidence and mortality are caused by risk factors such as smoking, unhealthy diet, excessive alcohol consumption, inactivity, and excess weight, and thus can be protected. CRC morbidity and mortality can also be reduced by proper screening and monitoring. Over the last few years the amalgamation of nanotechnology with healthcare system has brought about the potential to administer the delivery of certain therapeutic drugs to cancer cells without affecting normal tissues. Recent strategies combine the diagnostic and therapeutic approaches to improve the overall performance of cancer nanomedicines. Targeted cancer nanotherapeutics provides many more opportunities for the selective detection of toxic chemicals within cancer cells. The distinctive features of nanoparticles, such as their small size, large surface to volume ratio, and the ability of nanoparticles to achieve several interactions of ligands at surface, offer great benefits of nanomedicines to treat various types of cancers. This review highlights the molecular mechanisms of colorectal carcinogenesis and discusses various key concepts in the development of nanotherapeutics targeted for CRC treatment.

Extracellular Prostaglandins E1 and E2 and Inflammatory Cytokines Are Regulated by the Senescence Program in Potentially Premalignant Oral Keratinocytes.

Potentially pre-malignant oral lesions (PPOLs) are composed of keratinocytes that are either mortal (MPPOL) or immortal (IPPOL) in vitro. We report here that MPPOL, but not generally IPPOL, keratinocytes upregulate various extracellular tumor-promoting cytokines (interleukins 6 and 8) and prostaglandins E1 (ePGE1) and E2 (ePGE2) relative to normal oral keratinocytes (NOKs). ePGE upregulation in MPPOL was independent of PGE receptor status and was associated with some but not all markers of cellular senescence. Nevertheless, ePGE upregulation was dependent on the senescence program, cyclo-oxygenase 2 (COX2) and p38 mitogen-activated protein kinase and was partially regulated by hydrocortisone. Following senescence in the absence of p16INK4A, ePGEs accumulated in parallel with a subset of tumor promoting cytokine and metalloproteinase (MMP) transcripts, all of which were ablated by ectopic telomerase. Surprisingly, ataxia telangiectasia mutated (ATM) function was not required for ePGE upregulation and was increased in expression in IPPOL keratinocytes in line with its recently reported role in telomerase function. Only ePGE1 was dependent on p53 function, suggesting that ePGEs 1 and 2 are regulated differently in oral keratinocytes. We show here that ePGE2 stimulates IPPOL keratinocyte proliferation in vitro. Therefore, we propose that MPPOL keratinocytes promote the progression of IPPOL to oral SCC in a pre-cancerous field by supplying PGEs, interleukins and MMPs in a paracrine manner. Our results suggest that the therapeutic targeting of COX-2 might be enhanced by strategies that target keratinocyte senescence.

Lipid Engineered Nanoparticle Therapy for Burn Wound Treatment.

INTRODUCTION: Skin is the largest organ of the human body protecting the underlying organs and tissues from any foreign attack. Any damage caused in the skin may sometimes result in serious consequences within the internal body tissues. Burn is one such issue that damages the layers of the skin and thereby making the skin vulnerable and prone to any foreign matter entering and causing serious diseases. METHODS: An online literature assessment was steered for the lipid nanoparticles, burn wound treatments, and different types of nanoformulation. Appropriate information was taken from different electronic scientific databases such as Web of Science, Elsevier, Science Direct, Springer, PubMed, Google Scholar etc. Additional data was summarized from textbooks, local prints and scripts. RESULTS: Recent innovations and developments in nanotechnology-based drug delivery systems have shown promising results in minimizing the drawbacks associated with conventional therapies. Lipid based nanoparticles possess capabilities to deliver active agents to their target site without the possibility of degradation. Conventional therapy of burn wound is costly and the treatment is long lasting, making the patient uncomfortable. Moreover, it also doesn't yield satisfactory results or narrow effects. Encapsulation of bioactives inside the lipid core protects the active entity from pH and enzymatic degradations. CONCLUSION: This review highlights the drawbacks associated with conventional dosage forms. A lot of consideration is focused on the advancement of nanomaterials using innovative methods in wound care for treating burn wounds with a faster healing effect. This review article highlights recent developments in lipid based nanoformulations for the treatment of burn wound injury.

The role of YAP in the control of the metastatic potential of oral cancer.

The Yes-associated protein (YAP) is a downstream effector of the Hippo pathway and acts as a key transcription co-factor to regulate cell migration, proliferation, and survival. The Hippo pathway is evolutionarily conserved and controls tissue growth and organ size. Dysregulation and heterogeneity of this pathway are found in cancers, including oral squamous cell carcinoma (OSCC), leading to overexpression of YAP and its regulated proliferation machinery. The activity of YAP is associated with its nuclear expression and is negatively regulated by the Hippo kinase-mediated phosphorylation resulting in an induction of its cytoplasmic translocation. This review focuses on the role of YAP in OSCC in the context of cancer metastatic potential and highlights the latest findings about the heterogeneity of YAP expression and its nuclear transcription activity in oral cancer cell lines. The review also discusses the potential target of YAP in oral cancer therapy and the recent finding of the unprecedented role of the desmosomal cadherin desmoglein-3 (DSG3) in regulating Hippo-YAP signaling.

An insight on safety, efficacy, and molecular docking study reports of N-acetylcysteine and its compound formulations.

N-acetylcysteine (NAC) is considered as the body's major antioxidant molecules with diverse biological properties. In this review, the pharmacokinetics, safety and efficacy report on both the preclinical and clinical summary of NAC is discussed. Both in vitro and in vivo preclinical studies along with the clinical data have shown that NAC has enormous biological properties. NAC is used in the treatment of acetaminophen poisoning, diabetic nephropathy, Alzheimer's disease, schizophrenia, and ulcerative colitis, etc. Numerous analytical techniques, for instance, UPLC, LC-MS, HPLC, RP-IPC are primarily employed for the estimation of NAC in different single and fixed-dose combinations. The molecular docking studies on NAC demonstrate the binding within Sudlow's site-I hydrogen bonds and formation of NAC and BSA complexes. Various hydrophobic and hydrophilic amino acids generally exist in making contact with NAC as NAC-BSA complexes. Docking studies of NAC with the active site of the urease exposed an O-coordinated bond through nickel 3002 and a hydrogen bond through His-138. NAC and its analogs also made the allosteric pockets that helped to describe almost all favorable pose for the chaperone in a complex through the protein. Thus, we intended to highlight the several health benefits of this antioxidant compound and applications in pharmaceutical product development.

Exploring Nanoemulsions for Prostate Cancer Therapy.

Prostate carcinoma is typical cancer. It is the second most common cancer globally. The estimated new cases in 2020 was 191 930 and estimated deaths was 33 330. Age, family history, & genetic factors are major factors that drive prostate cancer. Although, for treating metastatic disease, the major therapies available are radiation,bisphosphonate, and palliative chemotherapy. But the major drawback is therapy is disease-driven and later becomes metastatic and requires treatment. The ability to revolutionize cancer treatment by major targeting vehicles via the exploration of nanoemulsion suggests a potential for cancer treatment. The unique property of a biphasic liquid dosage form called nanoemulsion to reach leaky tumor vasculature is due to its nano-meter oil-droplet size of 20-200 nm. Recent reporting on nanoemulsions disclose their embracing and lay alternative for re-purposing herbal and synthetic drugs and their combination especially for targeting prostate cancer formulating an obtainable nanomedicine. So, this article emphasizes the use of nanoemulsions incorporating therapeutic agents for successful and targeted delivery for prostate cancer.

Cerebroprotective effect of pterostilbene against global cerebral ischemia in rats.

AIM OF THE STUDY: The role of pterostilbene against induced neurobehavioral alterations in global cerebral ischemia-reperfusion and oxidative damage was studied. MATERIALS AND METHODS: Male SD rats (180-200 g) were exposed for 30 min to bilateral carotid artery occlusion accompanied by 60 min reperfusion to cause cerebral injury. Pretreatment with pterostilbene (200 and 400 mg/kg, orally) was given to the animals for ten days followed by ischemia-reperfusion injury. Various behavioral tests (locomotor activity, neurological score, transfer latency, hanging wire test) were studied. The brain tissues of animals were used for both the biochemical parameters (lipid peroxidation, reduced glutathione, superoxide dismutase, catalase activity) and histopathological study. RESULT: The pterostilbene as given orally significantly improved neurobehavioral alterations compared to control ischemia-reperfusion. Treatment with pterostilbene (200, and 400 mg/kg, orally) also significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione, and catalase activity as compared to control (ischemia-reperfusion) animals. Overall, pterostilbene treated animals showed non significant histological alteration as compared to ischemia-reperfusion control. CONCLUSION: This work suggests the beneficial effect of pterostilbene and its therapeutic potential against reperfusion-induced ischemia and associated behavioral changes in rats due to the stabilization of DNA damage with significant free radical scavenging properties.

Oxidative Stress-Mediated YAP Dysregulation Contributes to the Pathogenesis of Pemphigus Vulgaris.

Pemphigus Vulgaris (PV) is a life-threatening autoimmune disease manifested with blisters in the skin and mucosa and caused by autoantibodies against adhesion protein desmoglein-3 (Dsg3) expressed in epithelial membrane linings of these tissues. Despite many studies, the pathogenesis of PV remains incompletely understood. Recently we have shown Dsg3 plays a role in regulating the yes-associated protein (YAP), a co-transcription factor and mechanical sensor, and constraining reactive oxygen species (ROS). This study investigated the effect of PV sera as well as the anti-Dsg3 antibody AK23 on these molecules. We detected elevated YAP steady-state protein levels in PV cells surrounding blisters and perilesional regions and in keratinocytes treated with PV sera and AK23 with concomitant transient ROS overproduction. Cells treated with hydrogen peroxide also exhibited augmented nuclear YAP accompanied by reduction of Dsg3 and α-catenin, a negative regulator of YAP. As expected, transfection of α-catenin-GFP plasmid rendered YAP export from the nucleus evoked by hydrogen peroxide. In addition, suppression of total YAP was observed in hydrogen peroxide treated cells exposed to antioxidants with enhanced cell-cell adhesion being confirmed by decreased fragmentation in the dispase assay compared to hydrogen peroxide treatment alone. On the other hand, the expression of exogenous YAP disrupted intercellular junction assembly. In contrast, YAP depletion resulted in an inverse effect with augmented expression of junction assembly proteins, including Dsg3 and α-catenin capable of abolishing the effect of AK23 on Dsg3 expression. Finally, inhibition of other kinase pathways, including p38MAPK, also demonstrated suppression of YAP induced by hydrogen peroxide. Furthermore, antioxidant treatment of keratinocytes suppressed PV sera-induced total YAP accumulation. In conclusion, this study suggests that oxidative stress coupled with YAP dysregulation attributes to PV blistering, implying antioxidants may be beneficial in the treatment of PV.