Phycochemical and Biological Activities From Different Extracts of Padina antillarum (Kützing) Piccone.

Seaweeds are non-vascular, photosynthetic that inhabit the coastal regions commonly within rocky intertidal or submerged reef-like habitats and have been one of the richest and most promising sources of bioactive primary and secondary metabolites with antimicrobial properties. They selectively absorb elements like Na, K, Ca, Mg, I, and Br from the seawater and accumulate them in their thalli. Padina antillarum (Kützing) Piccone is a member of Phaeophycota and has remarkable phycochemistry as well as bioactivity. The phycochemical tests of the different extracts showed the presence of alkaloids, terpenoids, saponins, tannins, steroids, and phenols. The relative percentage of Oxirane, tetradecyl (C16H32O), and Cyclononasiloxane (C18H54O9Si9) are higher while Tetrasiloxane (C16H50O7Si8) is lowest in Gas Chromatography - Mass Spectrometry analysis. FRAP, %inhibition, the total antioxidant value of P. antillarum was higher in methanolic extract. Hexane, chloroform extracts showed no zone of inhibition against Bacillus subtilis, Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Staphylococcus epidermidis. The methanolic extract of P. antillarum exhibits a maximum zone of inhibition against S. epidermidis (18.66 ± 0.09). Antifungal activity of the P. antillarum in hexane extract exhibited no zone of inhibition against Aspergillus niger and Penicillium notatum while the chloroform extract yields maximum zone (37 ± 0.012, 21.66 ± 0.03). Diabetes mellitus is one of the most familiar chronic diseases associated with carbohydrate metabolism. It is also an indication of co-morbidities such as obesity, hypertension, and hyperlipidemia which are metabolic complications of both clinical and experimental diabetes. The treatment of P. antillarum methanol extract in mice reduced the body weight loss, low level of triglycerides, and elevated HDL cholesterol level as compared to diabetic mice.

Regulation of Cell-Signaling Pathways by Berbamine in Different Cancers.

Natural product research is a cornerstone of the architectural framework of clinical medicine. Berbamine is a natural, potent, pharmacologically active biomolecule isolated from Berberis amurensis. Berbamine has been shown to modulate different oncogenic cell-signaling pathways in different cancers. In this review, we comprehensively analyze how berbamine modulates deregulated pathways (JAK/STAT, CAMKII/c-Myc) in various cancers. We systematically analyze how berbamine induces activation of the TGF/SMAD pathway for the effective inhibition of cancer progression. We also summarize different nanotechnological strategies currently being used for proficient delivery of berbamine to the target sites. Berbamine has also been reported to demonstrate potent anti-cancer and anti-metastatic effects in tumor-bearing mice. The regulation of non-coding RNAs by berbamine is insufficiently studied, and future studies must converge on the identification of target non-coding RNAs. A better understanding of the regulatory role of berbamine in the modulation of non-coding RNAs and cell-signaling pathways will be advantageous in the effective translation of laboratory findings to clinically effective therapeutics.

Morpho-anatomical characterization of some members of euglenophycota (algae) of north-east Punjab, Pakistan based on light microscopy (LM) and scanning electron microscopy (SEM).

The study was carried out in four districts, that is, Gujranwala, Gujarat, Narowal and Sialkot of Punjab, Pakistan. The sampling was carried out randomly in different seasons from the water bodies especially from wastewater. Twenty-one species belonging to Euglenophycota were identified using light microscopy and scanning electron microscopy from which 04 species belong to genus Phacus, 02 species belonging to Trachelomonas and Euglena based on light microscopy. It was observed that Euglena was the most diverse genus and it is supposed to be the indicator species of the polluted water. It was observed that E. oblonga was found in maximum pH range, that is, 7.0-11.0. Similarly, E. brevicaudatus was found in maximum EC, that is, 169 ± 1.5 ms/cm these outcomes indicated that for internal examination along with LM, SEM was necessary for correct identification of algal sample up to specie level.

Antimetastatic effects of Citrus-derived bioactive ingredients: Mechanistic insights.

The growing complexity of metastasis has sparked tremendous interest in unraveling of the underlying mechanisms which play fundamental role in cancer progression and metastasis. Ground-breaking discoveries in metastasis research have greatly enhanced our understanding about intricate nature of metastasis. Bioactive chemicals obtained from citrus fruits have gained noteworthy appreciation because of significant cancer chemopreventive roles. Deregulated oncogenic signaling cascades play central role in metastasis. Emerging evidence has started to shed light on the metastasis inhibitory properties of naringin, naringenin, tangeretin, nobiletin, hesperidin and hesperetin in different cancer cell lines and xenografted mice. Wnt/?-catenin, TGF/SMAD and NOTCH signaling cascades have been shown to play linchpin role in carcinogenesis and metastasis. There is emerging evidence related to pharmacological targeting of Wnt/?-catenin, TGF/SMAD and NOTCH by citrus-derived bioactive components. These findings are indeed encouraging and will enable researchers to gain further insights into pharmacological targeting of oncogenic pathways to inhibit and prevent metastasis.

Regulation of cell signaling pathways by Schisandrin in different cancers: Opting for "Swiss Army Knife" instead of "Blunderbuss".

There has been an exponential growth in the field of molecular oncology and cutting-edge research has enabled us to develop a better understanding of therapeutically challenging nature of cancer. Based on the mechanistic insights garnered from decades of research, puzzling mysteries of multifaceted nature of cancer have been solved to a greater extent. Our rapidly evolving knowledge about deregulated oncogenic cell signaling pathways has allowed us to dissect different oncogenic transduction cascades which play critical role in cancer onset, progression and metastasis. Pharmacological targeting of deregulated pathways has attracted greater than ever attention in the recent years. Henceforth, discovery and identification of high-quality biologically active chemicals and products is gaining considerable momentum. There has been an explosion in the dimension of natural product research because of tremendous potential of chemopreventive and pharmaceutical significance of natural products. Schisandrin is mainly obtained from Schisandra chinensis. Schisandrin has been shown to be effective against different cancers because of its ability to inhibit/prevent cancer via modulation of different cell signaling pathways. Importantly, regulation of non-coding RNAs by schisandrin is an exciting area of research that still needs detailed and comprehensive research.   However, we still have unresolved questions about pharmacological properties of schisandrin mainly in context of its regulatory role in TGF/SMAD, SHH/GLI, NOTCH and Hippo pathways.

Regulation of cell signaling pathways by Wogonin in different cancers: Mechanistic review.

Natural products have historically been invaluable as a premium source of therapeutic agents. Recent advancements in genomics and structural biology have portrayed a high-resolution landscape of the diversity of proteins targeted by pharmacologically active products from natural sources. Natural product research has generated valuable wealth of information and cutting-edge research-works have leveraged our conceptual knowledge altogether to a new level. Wogonin (5,7-dihydroxy-8-methoxyflavone) is an O-methylated flavone and has attracted noteworthy appreciation because of its ability to pharmacologically target plethora of cell signaling pathways in different cancers. In this mini-review, we have gathered scattered pieces of available scientific evidence to summarize how wogonin pharmaceutically targeted Wnt/?-catenin, JAK/STAT, VEGF/VEGFR and TRAIL-driven apoptotic pathways in wide variety of cancers. We have also critically analyzed how wogonin prevented carcinogenesis and metastasis in tumor-bearing mice. Although researchers have uncovered pleiotropic role of wogonin in the regulation of different oncogenic signaling cascades but there are visible knowledge gaps in our understanding related to regulation of non-coding RNAs by wogonin. Future studies must converge on the unraveling of additional drug targets for wogonin to achieve a fuller and realistic understanding of the chemopreventive properties of wogonin.

Comparison of Urethrocutaneous Fistula Rate After Single Dartos and Double Dartos Tubularized Incised Plate Urethroplasty in Pediatric Hypospadias.

Background and objective Tubularized incised plate (TIP) urethroplasty is an easy and popular technique for repairing hypospadias, however urethrocutaneous fistula (UCF) is a frequently reported complication. Different techniques are used to reduce this complication. We aimed to compare the rate of UCF after single dartos and double dartos TIP urethroplasty in children with distal and mid penile hypospadias. Methods A randomized controlled trial (NCT04699318) was conducted in the Department of Pediatric Surgery, Mayo Hospital, Pakistan from August 2017 to February 2018, after ethical approval. After informed consent, a total of 60 patients with distal and mid penile hypospadias who were uncircumcised, had no chordee, and/or previous surgery, were randomly allocated in two groups using computer generated table numbers. Group A underwent single dartos TIP urethroplasty and Group B underwent double dartos TIP urethroplasty. Catheter was removed on day 10 post-operatively in both groups and primary outcome (UCF) was noted after a week of catheter removal. Rate of UCF was compared using chi square and p-value of <0.05 was taken as significant. Data was stratified to check for effect modifiers. Results Out of 60 children, eight (13.3%) developed UCF. In Group A, seven (23.3%) developed UCF and in Group B, one (3.3%) developed UCF (p-value 0.02). In both groups, no patient (0%) had urethral disruption, penile torsion, skin necrosis or meatal stenosis. Conclusion Additional covering of neo-urethra by a double dartos layer significantly reduces fistula rate after tubularized incised plate urethroplasty in both primary distal and mid penile hypospadias.

Association of Early-onset Androgenetic Alopecia and Metabolic Syndrome.

OBJECTIVE:  To evaluate the association of early-onset AGA (androgenetic alopecia) and metabolic syndrome in the younger male population. STUDY DESIGN: Case-control study. PLACE AND DURATION OF STUDY:  Department of Dermatology, Mayo Hospital Lahore, from October 2017 to March 2018. METHODOLOGY: A total of 202 patients were enrolled, 101 male patients with early-onset AGA (cases with a alopecia between 20-36 years of age), and were matched with 101 controls. All measurements regarding BMI, metabolic syndrome, and grades of alopecia were recorded on a pre-designed proforma. RESULTS: Of the 101 cases (mean age 27.77 ± 5.04 years), 27 (26.7%) had grade 3, 41 (40.6%) had grade 4, 29 (28.7%) had grade 5 and 4 (4%) had grade 6 AGA. Patients of AGA had an approximate four times increased frequency of metabolic syndrome. Of the cases 12 (11.9%) had metabolic syndrome whereas it was found in 3 (3%) of the control group. A significant association was found between cases of AGA and metabolic syndrome (p=0.016). CONCLUSION: This study suggests a significant association of AGA with metabolic syndrome. Key Words: Androgenetic alopecia, Metabolic syndrome, Early-onset alopecia, Cardiovascular disease.

Comparison of Ferguson and Gross herniotomy with Mitchell Banks' herniotomy in boys older than two years.

BACKGROUND & OBJECTIVE: In children younger than two years, most surgeons perform the inguinal herniotomy superficially through the external ring, a technique known as Mitchell-Banks' Herniotomy (MBH) while in older children, commonly Ferguson and Gross Herniotomy (FGH) is performed which involves opening of inguinal canal. Our aim was to compare the FGH and MBH in terms of recurrence in boys with inguinal hernia. METHODS: Boys with inguinal hernia presenting to Pediatric Surgery, Mayo Hospital Lahore from Dec 2016 to January 2018 were included in the study, if older than two years and younger than 14 years and without palpable deep ring (2 cm or more in width) or strangulation of inguinal hernia or malnutrition. They were randomly allocated in 2 groups after obtaining informed consent from parents, and underwent MBH (Group-A) and FGH (Group-B). Children were called for follow up after 1 week and at 6 months to assess for recurrence. RESULTS: Total 260 patients with inguinal hernia were enrolled (NCT: 03392636). The mean age of boys in Group-A was 5.2±3.0 years and in Group-B was 5.9±3.1 years. Mean operating time in Group-A (26.65±3.22 minutes) was longer than Group-B (15.92±4.22 minutes), and scrotal oedema was noted in 38 (29.2%) cases in Group-A, while 7 (5.4%) cases in Group-B. Testicular atrophy was noted in one patient of Group-B. Recurrence occurred in 1(0.8%) patient in Group-A, and in 8(6.2%) patients in Group-B (p-value 0.018). CONCLUSION: Mitchell-Banks' herniotomy has lower recurrence rate than Ferguson and Gross Herniotomy in boys older than two years.

Plant Defence Mechanisms Are Modulated by the Circadian System.

Plant health is an important aspect of food security, with pathogens, pests, and herbivores all contributing to yield losses in crops. Plants' defence against pathogens is complex and utilises several metabolic processes, including the circadian system, to coordinate their response. In this review, we examine how plants' circadian rhythms contribute to defence mechanisms, particularly in response to bacterial pathogen attack. Circadian rhythms contribute to many aspects of the plant-pathogen interaction, although significant gaps in our understanding remain to be explored. We conclude that if these relationships are explored further, better disease management strategies could be revealed.

Luteolin mediated targeting of protein network and microRNAs in different cancers: Focus on JAK-STAT, NOTCH, mTOR and TRAIL-mediated signaling pathways.

There has always been a keen interest of basic and clinical researchers to search for cancer therapeutics having minimum off-target effects and maximum anticancer activities. In accordance with this approach, there has been an explosion in the field of natural products research in the past few decades because of extra-ordinary list of natural extracts and their biologically and pharmacologically active constituents having significant medicinal properties. Apparently, luteolin-mediated anticancer effects have been investigated in different cancers but there is superfluousness of superficial data. Generalized scientific evidence encompassing apoptosis, DNA damage and anti-inflammatory effects has been reported extensively. However, how luteolin modulates deregulated oncogenic pathways in different cancers has not been comprehensively uncovered. In this review we have attempted to focus on cutting-edge research which has unveiled remarkable abilities of luteolin to modulate deregulated oncogenic pathways in different cancers. We have partitioned the review into various sections to separately discuss advancements in therapeutic targeting of oncogenic protein networks. We have provided detailed mechanistic insights related to JAK-STAT signaling and summarized how luteolin inhibited STAT proteins to inhibit STAT-driven gene network. We have also individually analyzed Wnt/ß-catenin and NOTCH pathway and how luteolin effectively targeted these pathways. Mapping of the signaling landscape has revealed that NOTCH pathway can be targeted therapeutically. NOTCH pathway was noted to be targeted by luteolin. We have also conceptually analyzed how luteolin restored TRAIL-induced apoptosis in resistant cancers. Luteolin induced an increase in pro-apoptotic proteins and efficiently inhibited anti-apoptotic proteins to induce apoptosis. Luteolin mediated regulation of non-coding RNAs is an exciting and emerging facet. Excitingly, there is sequential and systematic accumulation of clues which have started to shed light on intricate regulation of microRNAs by luteolin in different cancers. Collectively, sophisticated information will enable us to develop a refined understanding of the multi-layered regulation of signaling pathways and non-coding RNAs by luteolin in different cancers.

Vitamin C as an Anticancer Agent: Regulation of Signaling Pathways.

Treatment options for effective treatment of cancer with minimum off-target effects and maximum clinical outcomes have remained overarching goals in the clinical oncology. Vitamin C has remained in the shadows of controversy since the past few decades; burgeoning evidence has started to shed light on wide-ranging anticancer effects exerted by Vitamin C to induce apoptosis in drug-resistant cancer cells, inhibit uncontrolled proliferation of the cancer cells and metastatic spread. Landmark achievements in molecular oncology have ushered in a new era, and researchers have focused on the identification of oncogenic pathways regulated by Vitamin C in different cancers. However, there are visible knowledge gaps in our understanding related to the ability of Vitamin C to modulate a myriad of transduction cascades. There are scattered pieces of scientific evidence about promising potential of Vitamin C to regulate JAK-STAT, TGF/SMAD, TRAIL and microRNAs in different cancers. However, published data is insufficient and needs to be investigated comprehensively to enable basic and clinical researchers to reap full benefits and promote result-oriented transition of Vitamin C into various phases of clinical trials. In this review, we will emphasize on available evidence related to the regulation of oncogenic cell signaling pathways by Vitamin C in different cancers. We will also highlight the conceptual gaps, which need detailed and cutting-edge research.

Stromal vascular fraction-enriched platelet-rich plasma therapy reverses the effects of androgenetic alopecia.

BACKGROUND: Since antiquity, humans have been trying to devise remedies to cure androgenetic alopecia (AGA). These efforts include use of oral and topical concoctions and hair transplant strategies. As AGA affects people of all colors and creed, there has been a continuous effort to find a magic bullet against AGA. Unfortunately, to date, all the strategies to negate AGA effects have limitations and thus require new treatment options. AIM: To evaluate the efficacy of use of stromal vascular fraction (SVF) in androgenetic alopecia patients. METHODS: Stromal vascular fraction was obtained by enzymatic digestion of autologous adipose tissue. The patients were divided into two groups, that is, platelet-rich plasma (PRP) group and SVF-PRP group. In PRP group, only PRP was injected, while in SVF-PRP group a mixture of PRP and SVF was injected in affected scalp areas. After two sessions (4 weeks apart), the patients in both groups were assessed and analyzed using various parameters. RESULTS: Mean hair density in PRP group was increased from 52.44 hair/cm2 to 63.72 hair/cm2 (21.51% increase); while in SVF-PRP group, it was 37.66 hair/cm2 before treatment and 57.11 hair/cm2 after SVF-PRP therapy (51.64% increase). Percentage reduction in pull test was more significant in SVF-PRP group (80.78 ± 5.84) as compared to PRP group (34.01 ± 22.44). The physician and patient assessment scores also indicated a significant improvement in SVF-PRP group. CONCLUSION: A combined SVF-PRP therapy reversed effects of AGA more efficiently as compared to PRP therapy alone.

Role of mTORC1 and mTORC2 in Breast Cancer: Therapeutic Targeting of mTOR and Its Partners to Overcome Metastasis and Drug Resistance.

Based on the insights gleaned from decades of research, it seems clear that mechanistic target of rapamycin (mTOR) is an essential signaling node that integrates environmental clues for regulation of cell survival, metabolism and proliferation of the cells. However, overwhelmingly increasing scientific evidence has added a new layer of intricacy to already complicated and versatile signaling pathway of mTOR. Deregulation of spatio-temporally controlled mTOR-driven pathway played contributory role in breast cancer development and progression. Pharmacologists and molecular biologists have specifically emphasized on the identification and development of mTOR-pathway inhibitors. In this chapter we have attempted to provide an overview of the most recent findings related to therapeutic targeting of mTOR-associated mTORC1 and mTORC2 in breast cancer. We have also comprehensively summarized regulation of mTOR and its partners by microRNAs in breast cancer.

NEDD4 Family of E3 Ubiquitin Ligases in Breast Cancer: Spotlight on SMURFs, WWPs and NEDD4.

Massively parallel sequencing, genomic and proteomic technologies have provided near complete resolution of signaling landscape of breast cancer (BCa). NEDD4 family of E3-ubiquitin ligases comprises a large family of proteins particularly, SMURFs (SMURF1, SMURF2), WWPs and NEDD4 which are ideal candidates for targeted therapy. However, it is becoming progressively more understandable that SMURFs and NEDD4 have "split-personalities". These molecules behave dualistically in breast cancer and future studies must converge on detailed identification of context specific role of these proteins in BCa. Finally, we provide scattered clues of regulation of SMURF2 by oncogenic miRNAs, specifically considering longstanding questions related to regulation of SMURF1 and WWPs by miRNAs in BCa. SMURFS, WWPs and NEDD4 are versatile regulators and represent a fast-growing field in cancer research and better understanding of the underlying mechanisms will be helpful in transition of our knowledge from a segmented view to a more conceptual continuum.

Cutaneous manifestations in chronic myeloid leukemia in chronic phase treated with imatinib.

OBJECTIVE: The aim of this study was to see the patterns of skin changes in chronic myeloid leukemia (CML) in chronic phase treated with different doses of imatinib. METHODS: This cross-sectional study was conducted in the Oncology Department of Jinnah Hospital, Lahore, over a period of 6 months. Patients aged 7-70 years diagnosed either by fluorescence in situ hybridization (FISH) for BCR-ABL or cytogenetics for Philadelphia (Ph) chromosomes and consuming different doses of imatinib for the treatment of CML were randomly selected. Skin manifestations were analyzed and recorded on a predesigned proforma by a dermatologist. RESULTS: A total of 132 patients were enrolled; 65 male (49.24%) and 67 female (50.75%). Periorbital edema was found in 48.5% of cases, and hyperpigmentaion and melasma were found in 76.5% of cases. Pruritus was diagnosed in 6.8% of cases, alopecia in 5.3% of cases, and photosensitivity in 43.9% of cases. CONCLUSIONS: It was concluded that imatinib is associated with many adverse cutaneous side effects which should be overcome or reduced by either decreasing the duration of treatment with imatinib or switching to other treatment options.

Efficacy of platelet-rich plasma in androgenetic alopecia patients.

BACKGROUND: Androgenetic alopecia (AGA), a patterned hair loss in both males and females, is a commonly occurring disease worldwide. Conventionally, no curative or satisfactory treatment is available for this condition. Therefore, in the current study, we aim to use platelet-rich plasma (PRP) as an alternative treatment option for the AGA patients. MATERIALS AND METHODS: A total of 30 patients (20 men and 10 women) with AGA were included in the study between February 2017 and November 2017. Blood (9 cc) from each AGA patient was collected in 10 cc syringe, and PRP was isolated using commercially available kit under sterilized conditions. Isolated PRP was injected in the bald areas of scalp of AGA patients. The whole procedure was repeated after one month (two treatment sessions), and patients were followed for six months. The efficacy of PRP for restoration of hair was assessed using parameters such as hair density, terminal to vellus hair ratio, photographs, pull test, physician global assessment score, and patient global assessment score. RESULTS: Mean hair density on first visit (before treatment) was 34.18 ± 14.36/cm2 which was increased to 50.20 ± 15.91/cm2 after 6 months of first treatment (P value <0.05). On a scale of three, mean scores of physician and patient global assessments were 1.45 ± 0.57 and 1.60 ± 0.62, respectively. Mean percentage reduction of hair pulled was 29.2% (P value <0.05) after PRP treatment. Terminal to vellus hair ratio was increased in 60% of patients after PRP therapy. No remarkable adverse effects were noted in patients. CONCLUSION: Results showed that PRP is an effective treatment option in androgenetic alopecia as indicated by higher hair density, satisfactory physician and patient global assessment scores, and increase in terminal to vellus hair ratio.

Emerging themes of regulation of oncogenic proteins by Solanum nigrum and its bioactive molecules in different cancers.

Research over the decades has sequentially and systematically provided a near-complete resolution of multifaceted and therapeutically challenging nature of cancer. Drug discovery from plants has enjoyed a renaissance in the past few years. Natural products have provided many of the lead structures, which are currently being used as templates for the design and synthesis of novel compounds with biologically enhanced properties. With the maturity and diversification of technologies, there is a growing need to design high-throughput functional assays for the evaluation of the myriad of compounds being catalogued. This review sheds light on the tumor suppressive properties of Solanum nigrum and its bioactive ingredients. Several worthy of mention include uttroside B, solanine, solamargine, and physalins, which have been tested for efficacy in cancer cell lines and xenografted mice. We have summarized the most recent findings related to S. nigrum-mediated regulation of intracellular protein network in different cancers. α-Solanine, an active component of S. nigrum, is involved in the regulation of microRNA-21 (miRNA-21) (oncogenic) and miRNA-138 (tumor suppressor) in prostate cancer. However, this is the only available evidence that gives us a clue related to the tumor suppressive effects exerted by components of S. nigrum at a posttranscriptional level. More interestingly, S. nigrum and its components exerted inhibitory effects on different pathways including PI3K/AKT, JAK-STAT, VEGF/VEGFR, and matrix metalloproteinases in different cancers. We also provide an overview of new tools, methodologies, and approaches, which will allow researchers to extract as much information as possible out of the tremendous data sets currently being generated. The use of computational tools will be helpful in processing structurally complex natural products and also in prediction of their macromolecular targets.

Factors Affecting Dermatological Manifestations in Patients with End Stage Renal Disease.

OBJECTIVE: To determine skin changes in patients of End Stage Renal Disease (ESRD) on maintenance hemodialysis (MHD) and factors affecting these changes. STUDY DESIGN: Cross-sectional observational study. PLACE AND DURATION OF STUDY: Nephrology Department, Mayo Hospital, Lahore in collaboration with Dermatology Department, King Edward Medical University, Lahore, from October 2015 to January 2016. METHODOLOGY: Two hundred patients who were undergoing MHD for more than three months were included in the study. Patients' demographic data, laboratory reports and dialysis records were noted in a predesigned questionnaire. Skin examination was carried out by consultant dermatologist after patient's permission. RESULTS: Among 200 patients included in study, 105 were malesand rest of them were females. Major causes of ESRD were Diabetes Mellitus (n=83, 41.5%, followed by Hypertension (n=80, 40%), Nephrolithiasis (n=15, 7.5%) and Chronic glomerulonephritis (n=5, 2.5%). At least one cutaneous finding was present in every patient. Common skin findings observed were pigmentation (86%), xerosis (83%), pallor (79%), pruritus (69%), acquired ichthyosis (50.5%), and bacterial skin infections (18.5%). Among them, nail manifestations were half-and-half nails (52%), onychomycosis (30.5%), onycholysis (20.5%), subungual hyperkeratosis (23.5%), and Mee's lines (7.5). Among hair changes were sparse scalp hair (38.5%), brittle and lustreless hair (28%). The factors contributing to skin changes were patient's age, cause of ESRD, anti HCV positivity, high urea and creatinine levels, duration and frequency of hemodialysis, hemoglobin levels, calcium phosphate product and socioeconomic status. Some skin manifestations were interrelated with each other like xerosis with pruritus (p<0.001), pruritus with bacterial infection (p<0.022), acquired Ichthyosis (p=0.008) and hair changes (p=0.035). CONCLUSION: ESRD patients on hemodialysis develop various skin changes during the course of disease process, which contribute to increased morbidity. Different factors affecting skin changes were the cause of ESRD, adequacy and duration of dialysis, employment, financial status, anti HCV positivity, and metabolic factors.

Regulation of signal transduction cascades by Pterostilbenes in different cancers: Is it a death knell for oncogenic pathways.

Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks. In this review, we chronicle the milestone achievements and discuss how Pterostilbenes effectively regulated different cellular pathways. We have provided detailed mechanistic insights related to regulation of JAK-STAT signaling, Notch pathway, Wnt mediated intracellular signaling by pterostilbene. Underlying mechanisms about regulation of PI3K/AKT and MAPK pathways by pterostilbene in different cancers.  Regulation of Metastasis-associated protein 1 (MTA1) proteins and Human telomerase reverse transcriptase (hTERT) in cancer cells by pterostilbene. Pterostilbene has also been reported to modulate the expression of various oncogenic and tumor suppressor microRNAs in cancer cells. Better and sharper comprehension of the concepts associated with the modes of action of pterostilbene in different cancers will be useful in identification of cancers which can be efficiently targeted by pterostilbene.