Growth, haemato-biochemical, hormonal and disease characteristics in Black Bengal goats: a review.

The goats have been considered one of the noteworthy animals to provide food security and could promote socio-economic upliftment under challenging climatic scenarios in the coming decades, particularly in the tropics. Black Bengal goat (BBG) is one of the recognised native meat-type breeds of hot-humid tropics with distinguished characteristics, including superior-quality meat, excellent skin and high prolificacy. Smaller body mass, lower metabolic rate and efficient utilisation of high-fibre forages enable BBG to adapt to a wide range of harsh climates in the tropics. The BBG can maintain physiological homeostasis efficiently in terms of electrolyte profile, endocrine functions and haemato-biochemical traits in different life phases, including the gestation period, even in high-saline coastal areas of hot-humid tropics. Crossbreeding to improve its growth rate has been attempted, but the prolificacy has been decayed. This review is intended to attract global attention to the adaptive potentialities of Black Bengal goats in terms of growth and production, haemato-biochemical, endocrinological, salt tolerance and disease characteristics that could be an asset of climate-resilient agricultural farming.

Effect of dietary oregano essential oil and milk replacer on physiological status and immunological responses of pre- and post-weaned Ghoongroo piglets.

Ghoongroo pigs have good adaptability in a low input production system with high prolificacy. The present study was conducted on pre-and post-weaned Ghoongroo piglets from 2-3 days to 12 weeks of age to evaluate the effect of a milk replacer and oregano essential oil (EO) on growth, physiological and immunological responses. Thirty six piglets were randomly divided into three groups. The control group (n = 12) was allowed to suck mother's milk. Second group piglets were provided milk replacer (MR) and piglets of the third group were provided milk replacer along with oregano EO at 500 mg/kg diet. After weaning, piglets were provided standard concentrate diets. The results showed that the body weight in MR and MR + EO groups were significantly higher compared with the control. The MR + EO group had better intestinal microbiota, greater nonspecific innate immunity with the phagocytosis efficacy of neutrophils, lower cortisol concentration and more stable thyroid hormones than the other groups. The better haematological status supported the rapid organ development and improved intestinal health status in both the experimental groups. In conclusion, milk replacer, especially with the inclusion of oregano EO, can lower weaning stress, enhance nonspecific immunity and improve growth and health status of piglets.

Tunicamycin-induced ER stress in breast cancer cells neither expresses GRP78 on the surface nor secretes it into the media.

GRP78 (an Mr 78 kDa calcium dependent glucose binding protein) is located in ER lumen. It functions as ER chaperone and translocates proteins for glycosylation at the asparagine residue present in the sequon Asn-X-Ser/Thr. Paraffin sections from N-glycosylation inhibitor tunicamycin treated ER-/PR-/HER2+ (double negative) breast tumor in athymic nude mice exhibited reduced N-glycan but increased GRP78 expression. We have evaluated the effect of tunicamycin on cellular localization of GRP78 in metastatic human breast cancer cells MDA-MB-231 (ER-/PR-/HER2-). Tunicamycin inhibited cell proliferation in a time and dose-dependent manner. Nonmetastatic estrogen receptor positive (ER+) MCF-7 breast cancer cells were also equally effective. GRP78 expression (protein and mRNA) was higher in tunicamycin (1.0 µg/mL) treated MCF-7 and MDA-MB-231 cells. GRP78 is an ER stress marker, so we have followed its intracellular localization using immunofluorescence microscopy after subjecting the cancer cells to various stress conditions. Unfixed cells stained with either FITC-conjugated Concanavalin A (Con A) or Texas-red conjugated wheat germ agglutinin (WGA) exhibited surface expression of N-glycans but not GRP78. GRP78 became detectable only after a brief exposure of cells to ice-cold methanol. Western blotting did not detect GRP78 in conditioned media of cancer cells whereas it did for MMP-1. The conclusion, GRP78 is expressed neither on the outer-leaflet of the (ER-/PR-/HER2-) human breast cancer cells nor it is secreted into the culture media during tunicamycin-induced ER stress. Our study therefore suggests strongly that anti-tumorigenic action of tunicamycin can be modeled to develop next generation cancer therapy, i.e., glycotherapy for treating breast and other sold tumors.

Dynamic Function of DPMS Is Essential for Angiogenesis and Cancer Progression.

Dolichol phosphate mannose synthase (DPMS) is an inverting GT-A-folded enzyme and classified as GT2 by CAZy. DPMS sequence carries a metal-binding DXD motif, a PKA motif, and a variable number of hydrophobic domains. Human and bovine DPMS possess a single transmembrane domain, whereas that from S. cerevisiae and A. thaliana carry multiple transmembrane domains and are superimposable. The catalytic activity of DPMS is documented in all spheres of life, and the 32kDa protein is uniquely regulated by protein phosphorylation. Intracellular activation of DPMS by cAMP signaling is truly due to the activation of the enzyme and not due to increased Dol-P level. The sequence of DPMS in some species also carries a protein N-glycosylation motif (Asn-X-Ser/Thr). Apart from participating in N-glycan biosynthesis, DPMS is essential for the synthesis of GPI anchor as well as for O- and C-mannosylation of proteins. Because of the dynamic nature, DPMS actively participates in cellular proliferation enhancing angiogenesis and breast tumor progression. In fact, overexpression of DPMS in capillary endothelial cells supports increased N-glycosylation, cellular proliferation, and enhanced chemotactic activity. These are expected to be completely absent in congenital disorders of glycosylation (CDGs) due to the silence of DPMS catalytic activity. DPMS has also been found to be involved in the cross talk with N-acetylglucosaminyl 1-phosphate transferase (GPT). Inhibition of GPT with tunicamycin downregulates the DPMS catalytic activity quantitatively. The result is impairment of surface N-glycan expression, inhibition of angiogenesis, proliferation of human breast cancer cells, and induction of apoptosis. Interestingly, nano-formulated tunicamycin is three times more potent in inhibiting the cell cycle progression than the native tunicamycin and is supported by downregulation of the ratio of phospho-p53 to total-p53 as well as phospho-Rb to total Rb. DPMS expression is also reduced significantly. However, nano-formulated tunicamycin does not induce apoptosis. We, therefore, conclude that DPMS could become a novel target for developing glycotherapy treating breast tumor in the clinic.

Dolichol phosphate mannose synthase: a Glycosyltransferase with Unity in molecular diversities.

N-glycans provide structural and functional stability to asparagine-linked (N-linked) glycoproteins, and add flexibility. Glycan biosynthesis is elaborative, multi-compartmental and involves many glycosyltransferases. Failure to assemble N-glycans leads to phenotypic changes developing infection, cancer, congenital disorders of glycosylation (CDGs) among others. Biosynthesis of N-glycans begins at the endoplasmic reticulum (ER) with the assembly of dolichol-linked tetra-decasaccharide (Glc3Man9GlcNAc2-PP-Dol) where dolichol phosphate mannose synthase (DPMS) plays a central role. DPMS is also essential for GPI anchor biosynthesis as well as for O- and C-mannosylation of proteins in yeast and in mammalian cells. DPMS has been purified from several sources and its gene has been cloned from 39 species (e.g., from protozoan parasite to human). It is an inverting GT-A folded enzyme and classified as GT2 by CAZy (carbohydrate active enZyme; http://www.cazy.org ). The sequence alignment detects the presence of a metal binding DAD signature in DPMS from all 39 species but finds cAMP-dependent protein phosphorylation motif (PKA motif) in only 38 species. DPMS also has hydrophobic region(s). Hydropathy analysis of amino acid sequences from bovine, human, S. crevisiae and A. thaliana DPMS show PKA motif is present between the hydrophobic domains. The location of PKA motif as well as the hydrophobic domain(s) in the DPMS sequence vary from species to species. For example, the domain(s) could be located at the center or more towards the C-terminus. Irrespective of their catalytic similarity, the DNA sequence, the amino acid identity, and the lack of a stretch of hydrophobic amino acid residues at the C-terminus, DPMS is still classified as Type I and Type II enzyme. Because of an apparent bio-sensing ability, extracellular signaling and microenvironment regulate DPMS catalytic activity. In this review, we highlight some important features and the molecular diversities of DPMS.

Changes in expression of monocarboxylate transporters, heat shock proteins and meat quality of Large White Yorkshire and Ghungroo pigs during hot summer period.

OBJECTIVE: Present study explores the effect of hot summer period on the glycolytic rate of early post-mortem meat quality of Ghungroo and Large White Yorkshire (LWY) pig and comparative adaptability to high temperature between above breeds by shifting the expression of stress related genes like mono-carboxylate transporters (MCTs) and heat shock proteins (HSPs). METHODS: Healthy pigs of two different breeds, viz., LYW and Ghungroo (20 from each) were maintained during hot summer period (May to June) with a mean temperature of about 38°C. The pigs were slaughtered and meat samples from the longissimus dorsi (LD) muscles were analyzed for pH, glycogen and lactate content and mRNA expression. Following 24 h of chilling, LD muscle was also taken from the carcasses to evaluate protein solubility and different meat quality measurements. RESULTS: LWY exhibited significantly (p<0.01) higher plasma cortisol and lactate dehydrogenase concentration than Ghungroo indicating their higher sensitivity to high temperature. LD muscle from LWY pigs revealed lower initial and ultimate pH values and higher drip loss compared to Ghungroo, indicating a faster rate of pH fall. LD muscle of Ghungroo had significantly lower lactate content at 45 min postmortem indicating normal postmortem glycolysis and much slower glycolytic rate at early postmortem. LD muscle of LWY showed rapid postmortem glycolysis, higher drip loss and higher degrees of protein denaturation. Ghungroo exhibited slightly better water holding capacity, lower cooking loss and higher protein solubility. All HSPs (HSP27, HSP70, and HSP90) and MCTs (MCT1, MCT2, and MCT4) in the LD muscle of pigs inclined to increase more in Ghungroo than LWY when exposed to high temperature. CONCLUSION: Effect of high temperature on the variation of HSPs and MCTs may play a crucial role in thermal tolerance and adaptation to different climatic conditions, pH regulation, muscle acidification, drip loss, protein denaturation and also in postmortem meat quality development.

Copy number differences of Y chromosomal genes between superior and inferior quality semen producing crossbred (Bos taurus × Bos indicus) bulls.

The removal of crossbred bulls from semen collection programs due to the production of poor quality semen causes substantial monetary losses to the dairy industry. Seminal quality, a quantitative trait, is greatly influenced by genome level variations. Deletion and/or duplication of Y chromosomal genes and subsequent changes in gene copy number have a major role in determining spermatogenic efficiency and, therefore, seminal quality. In this study, copy numbers of three Y chromosomal genes TSPY, DDX3Y, and USP9Y in genomic DNA were estimated and compared in two groups of crossbred (Bos taurus × Bos indicus) bulls of ten each, superior and inferior quality semen producing bulls, which were classified based on their seminal quality parameters. For TSPY gene, the inferior quality semen donor group has significantly lower copy number than superior quality semen donor group (p < 0.05). No significant difference was found in DDX3Y and USP9Y gene copy numbers between two groups (p > 0.05). In conclusion, this study demonstrates that the copy number of TSPY, a Y chromosomal spermatogenesis related gene, may be an important determinant to predict the quality of bull semen, facilitating better selection of bulls in a herd for semen collection program.

Efficacy of Saccharomyces cerevisiae Fermentation Product and Probiotic Supplementation on Growth Performance, Gut Microflora and Immunity of Broiler Chickens.

Concern for global health security and the environment due to the emergence of antibiotic-resistant bacteria and antibiotic residues in meat and other livestock products has led many countries to restrict the use of antibiotics in animal feed. This experiment was performed to assess the impact of dietary supplementation of a probiotic (Bacillus subtilis) and a postbiotic (Saccharomyces cerevisiae fermentation product) on growth performance, carcass traits, blood haemato-biochemical profile, gut microflora, gut morphology, and immune response in broilers as an alternative to antimicrobials in poultry production system to minimize the effect on global health security. A total of 324 one-day-old Ven Cobb 400 broiler chicks were randomly divided into three dietary groups, each containing 12 replicated pens, and each replicate contained nine chickens. The dietary groups consisted of (1) a basal diet without any growth promoters (T1), (2) the basal diet augmented with Bacillus subtilis at 200 g/MT feed (T2), and (3) the basal diet supplemented with Saccharomyces cerevisiae fermentation product at 1.25 kg/MT feed (T3). To calculate body weight gain, all birds and residual feed were weighed on a replicated basis on days 0, 7, 14, 21, 28, 35, and 42; mortality was recorded daily. At the end of the trial (42 d), two chickens from each replicate were slaughtered for carcass traits, gut microflora, and morphology measurements. Blood samples were collected for the haemato-biochemical profile on 35 d and antibody titer on 28 d and 35 d. Feeding with SCFP (T3 group) significantly improved average daily feed intake (ADFI) and average daily gain (ADG) of chickens compared to the T1 (control) and T2 (probiotic) groups from 1 to 14 days of age. Feed conversion ratio (FCR) was significantly improved in SCFP-fed birds (T3) relative to the control (T1) over the entire experimental period. Carcass traits and blood haemato-biochemical parameters remained unaffected by any diets. However, cholesterol levels and concentrations of corticosterone were significantly lower in T3 compared to T2 and T1 groups. Total E. coli, Enterohaemorrhagic E. coli, ESBL-producing Enterobacteriaceae, and Salmonella counts were significantly lower in T2 and T3 groups compared to T1 group and Salmonella counts were lower in T3 when compared to T2. However, there was no significant difference in Lactobacillus count among treatment groups. A significant increase in villi height and villi-height-to-crypt-depth ratio (VH: CD) was observed in both T3 and T2 groups. On day 28, the T3 and T2 groups exhibited a significant increase in antibody titers against Newcastle disease virus and infectious bursal disease virus. It can be concluded that Saccharomyces cerevisiae fermentation product and Bacillus subtilis probiotic could be viable alternatives to antimicrobials in poultry production considering beneficial impacts in broilers fed an antibiotic-free diet.

N-glycans in cell survival and death: cross-talk between glycosyltransferases.

Asparagine-linked (N-linked) protein glycosylation is one of the most important protein modifications. N-glycans with "high mannose", "hybrid", or "complex" type sugar chains participate in a multitude of cellular processes. These include cell-cell/cell-matrix/receptor-ligand interaction, cell signaling/growth and differentiation, to name a few. Many diseases such as disorders of blood clotting, congenital disorder of glycosylation, diseases of blood vessels, cancer, neo-vascularization, i.e., angiogenesis essential for breast and other solid tumor progression and metastasis are associated with N-glycan expression. Biosynthesis of N-glycans requires multiple steps and multiple cellular compartments. Following transcription and translation the proteins migrate to the endoplasmic reticulum (ER) lumen to acquire glycan chain(s) with a defined glycoform, i.e., a tetradecasaccharide. These are further modified, i.e., edited in ER lumen and in Golgi prior to moving to their respective destinations. The tetradecasaccharide is pre-assembled on a poly-isoprenoid lipid called dolichol, and becomes an essential component of the supply chain. Therefore, dolichol cycle synthesizing the lipid-linked oligosaccharide (LLO) is a hallmark for all N-linked glycoproteins. It is expected that there is a great deal of cross-talk between the participating glycosyltransferases and any missed step would express defective N-glycans that could have fatal consequences. The positive impact of the structurally altered N-glycans could lead to discovery of an N-glycan signature for a disease and/or help developing glycotherapeutic treating cancer or other human diseases. The purpose of this review is to identify the gaps of N-glycan biology and help developing appropriate technology for biomedical applications. This article is part of a Special Issue entitled Glycoproteomics.

BIRTH OF A GLYCOTHERAPY FOR BREAST CANCER.

Breast cancer is the most common malignant disease in women and is worldwide. The incidence rate of women's breast cancer in 2020 was 2,261,419 and 2022 estimates diagnosing 1,918,030 cases. The disease is heterogeneous and the pathogenesis of breast cancer still remains unclear. Much progress has been made in early detection and better treatment to improve survival. Unfortunately, the current treatment strategies destroy the patient's quality of life. The patients develop drug resistance, exhibit severe side effects, and not afford the cost creates anxiety among the patients, families, and friends. In addition, a considerable number of patients relapse as a result of organ metastasis, e.g., the triple-negative breast cancer (TNBC, ER-/PR-HER2-). The 5-year survival rate of patients who recurred with distant metastasis is less than 20%. More than half a million women worldwide still suffer from metastatic breast cancer annually, and 90% of their deaths could be attributed to metastasis. One of the reasons for the failure of cancer therapeutics is the approaches did not consider the cancer holistically. All breast cancer cells and their micro environmental capillary endothelial cells express asparagine-linked (N-linked) glycoproteins. We have tested a biologic and a small molecule, Tunicamycin-P (P = pure N-glycosylation inhibitor) to interfere with the protein N-glycosylation pathway in the endoplasmic reticulum (ER) by specifically blocking the catalytic activity of N-acetylglusosaminyl 1-phosphate transferase (GPT) activity. The outcome has been quantitative inhibition of in vitro and in vivo angiogenesis and the breast tumor progression of multiple subtypes in pre-clinical mouse models with "zero" toxicity. We have, therefore, concluded that Tunicamycin-P is expected to supersede the current therapeutics and become a Glycotherapy treating breast cancer of all subtypes.

Canine umbilical cord tissue derived mesenchymal stem cells naturally express mRNAs of some antimicrobial peptides.

Antimicrobial peptides (AMPs) are naturally produced by all living organisms at a constitutive rate. They represent the first line of active defence systems against invading microorganisms, helping in innate immunity. Besides their therapeutic applications, great attention has also been given to the mesenchymal stem cells (MSCs) due to their antimicrobial activities. The study aimed to observe the mRNA expression profile of few antimicrobial peptides (AMPs) in canine MSCs during standard in vitro culture. MSCs were isolated from canine umbilical cord tissue, propagated and characterized by morphology, surface markers and tri-lineage differentiation capability. The mRNA expression of eleven commonly known antimicrobial peptides was checked by Reverse Transcriptase PCR. It has been found for the first time that canine MSCs naturally express the mRNAs of AMPs like C-X-C motif chemokine ligand 8 (CXCL8), Elafin (PI3), Hepcidin (HAMP), Lipocalin 2 (LCN2) and Secretory leukocyte protease inhibitor (SLPI). However, their expressions at protein level and, relation with antimicrobial effect of canine MSCs need to be explored.

Characterization of interferon gamma gene in relation to immunological responses in Haemonchus contortus resistant and susceptible Garole sheep.

Garole sheep exhibits within-breed difference in resistance to natural gastrointestinal nematode infection predominated by Haemonchus contortus. In the present study, interferon gamma gene (IFN-γ) was characterized in relation to parasitological, haematological, and immune response against H. contortus in resistant and susceptible Garole sheep. Resistant and susceptible Garole sheep were selected from the field based on consistent low faecal egg counts (FEC) for one year and single nucleotide polymorphisms (SNPs) in the IFN-γ gene. The partial amplification of IFN-γ gene (1282 bp) revealed 4 SNPs exclusively in resistant sheep and 3 SNPs were shared between resistant and susceptible Garole sheep. The selected resistant and susceptible Garole sheep were challenged with H. contortus infection. The parasitological, haematological, immunological responses, and expression of IFN-γ gene were compared between the resistant and susceptible Garole sheep. The FEC of resistant sheep was significantly (P < 0.05) lower than the susceptible sheep infected with H. contortus. There was spontaneous elimination of H. contortus from 28 to 33 days post infection (DPI) in resistant sheep. Haemoglobin and packed cell volume were significantly (P < 0.05) higher in resistant sheep than the susceptible sheep. The serum concentration of immunoglobulin (Ig)G1 and IgA and cytokine IFN-γ activity and also the expression of IFN-γ gene were significantly (P < 0.05) higher in the infected resistant sheep from 14 to 28 DPI compared to the susceptible sheep. In resistant sheep, IgA and IgG1 and cytokine IFN-γ positively correlated with expression of IFN-γ gene, and the SNPs recorded in the resistant sheep only might play an important role in conferring resistance against H. contortus. Further studies are required to elucidate the role of IFN-γ gene in H. contortus resistance in Garole sheep.

Unfolded protein response is required in nu/nu mice microvasculature for treating breast tumor with tunicamycin.

Up-regulation of the dolichol pathway, a "hallmark" of asparagine-linked protein glycosylation, enhances angiogenesis in vitro. The dynamic relationship between these two processes is now evaluated with tunicamycin. Capillary endothelial cells treated with tunicamycin were growth inhibited and could not be reversed with exogenous VEGF(165). Inhibition of angiogenesis is supported by down-regulation of (i) phosphorylated VEGFR1 and VEGFR2 receptors; (ii) VEGF(165)-specific phosphotyrosine kinase activity; and (iii) Matrigel(TM) invasion and chemotaxis. In vivo, tunicamycin prevented the vessel development in Matrigel(TM) implants in athymic Balb/c (nu/nu) mice. Immunohistochemical analysis of CD34 (p < 0.001) and CD144 (p < 0.001) exhibited reduced vascularization. A 3.8-fold increased expression of TSP-1, an endogenous angiogenesis inhibitor in Matrigel(TM) implants correlated with that in tunicamycin (32 h)-treated capillary endothelial cells. Intravenous injection of tunicamycin (0.5 mg/kg to 1.0 mg/kg) per week slowed down a double negative (MDA-MB-435) grade III breast adenocarcinoma growth by ∼50-60% in 3 weeks. Histopathological analysis of the paraffin sections indicated significant reduction in vessel size, the microvascular density and tumor mitotic index. Ki-67 and VEGF expression in tumor tissue were also reduced. A significant reduction of N-glycan expression in tumor microvessel was also observed. High expression of GRP-78 in CD144-positive cells supported unfolded protein response-mediated ER stress in tumor microvasculature. ∼65% reduction of a triple negative (MDA-MB-231) breast tumor xenograft in 1 week with tunicamycin (0.25 mg/kg) given orally and the absence of systemic and/or organ failure strongly supported tunicamycin's potential for a powerful glycotherapeutic treatment of breast cancer in the clinic.

Balancing life with glycoconjugates: monitoring unfolded protein response-mediated anti-angiogenic action of tunicamycin by Raman Spectroscopy.

Asparagine-linked protein glycosylation is a hallmark for glycoprotein structure and function. Its impairment by tunicamycin [a competitive inhibitor of N-acetylglucosaminyl 1-phosphate transferase (GPT)] has been known to inhibit neo-vascularization (i.e., angiogenesis) in humanized breast tumor due to an induction of ER stress-mediated unfolded protein response (UPR). The studies presented here demonstrate that (i) tunicamycin (i) inhibits capillary endothelial cell proliferation in a dose dependent manner; (ii) treated cells are incapable of forming colonies upon its withdrawal; and (iii) tunicamycin treatment causes nuclear fragmentation. Tunicamycin-induced ER stress-mediated UPR event in these cells was studied with the aid of Raman spectroscopy, in particular, the interpretation of bands at 1672, 1684 and 1694 cm(-1), which are characteristics of proteins and originate from C=O stretching vibrations of mono-substituted amides. In tunicamycin-treated cells these bands decreased in area as follows: at 1672 cm(-1) by 41.85% at 3 h and 55.39% at 12 h; at 1684 cm(-1) by 20.63% at 3 h and 40.08% at 12 h; and also at 1994 cm(-1) by 33.33% at 3 h and 32.92% at 12 h, respectively. Thus, in the presence of tunicamycin, newly synthesized protein chains fail to arrange properly into their final secondary and/or tertiary structures, and the random coils they form had undergone further degradation.

Glycotherapy: A New Paradigm in Breast Cancer Research.

Breast cancer is an ancient disease recognized first by the Egyptians as early as 1600 BC. The first cancer-causing gene in a chicken tumor virus was found in 1970. The United States signed the National Cancer Act in 1971, authorizing federal funding for cancer research. Irrespective of multi-disciplinary approaches, diverting a great deal of public and private resources, breast cancer remains at the forefront of human diseases, affecting as many as one in eight women during their lifetime. Because of overarching challenges and changes in the breast cancer landscape, five-year disease-free survival is no longer considered adequate. The absence of a cure, and the presence of drug resistance, severe side effects, and destruction of the patient's quality of life, as well as the fact that therapy is often expensive, making it unaffordable to many, have created anxiety among patients, families, and friends. One of the reasons for the failure of cancer therapeutics is that the approaches do not consider cancer holistically. Characteristically, all breast cancer cells and their microenvironmental capillary endothelial cells express asparagine-linked (N-linked) glycoproteins with diverse structures. We tested a small biological molecule, Tunicamycin, that blocks a specific step of the protein N-glycosylation pathway in the endoplasmic reticulum (ER), i.e., the catalytic activity of N-acetylglusosaminyl 1-phosphate transferase (GPT). The outcome was overwhelmingly exciting. Tunicamycin quantitatively inhibits angiogenesis in vitro and in vivo, and inhibits the breast tumor progression of multiple subtypes in pre-clinical mouse models with "zero" toxicity. Mechanistic details support ER stress-induced unfolded protein response (upr) signaling as the cause for the apoptotic death of both cancer and the microvascular endothelial cells. Additionally, it interferes with Wnt signaling. We therefore conclude that Tunicamycin can be expected to supersede the current therapeutics to become a glycotherapy for treating breast cancer of all subtypes.

Waste-derived biomaterials as building blocks in the biomedical field.

Recent developments in the biomedical arena have led to the fabrication of innovative biomaterials by utilizing bioactive molecules obtained from biological wastes released from fruit and beverage processing industries, and fish, meat, and poultry industries. These biological wastes that end up in water bodies as well as in landfills are an affluent source of animal- and plant-derived proteins, bio ceramics and polysaccharides such as collagens, gelatins, chitins, chitosans, eggshell membrane proteins, hydroxyapatites, celluloses, and pectins. These bioactive molecules have been intricately designed into scaffolds and dressing materials by utilizing advanced technologies for drug delivery, tissue engineering, and wound healing relevance. These biomaterials are environment-friendly, biodegradable, and biocompatible, and show excellent tissue regeneration attributes. Additionally, being cost-effective they can reduce the burden on the healthcare system as well as provide a sustainable solution to waste management. In this review, the current trends in the utilization of plant and animal waste-derived biomaterials in various biomedical fields are considered along with a separate section on their applications as xenografts.

RFamide peptides, the novel regulators of mammalian HPG axis: A review.

The RFamide-related peptides (RFRPs) are the group of neuropeptides synthesized predominantly from the hypothalamus that negatively affects the hypothalamo-hypophyseal-gonadal (hypothalamic-pituitary-gonadal [HPG]) axis. These peptides are first identified in quail brains and emerged as the mammalian orthologs of avian gonadotropin inhibitory hormones. The RFRP-3 neurons in the hypothalamus are present in several mammalian species. The action of RFRP-3 is mediated through a G-protein-coupled receptor called OT7T022. The predominant role of RFRP-3 is the inhibition of HPG axis with several other effects such as the regulation of metabolic activity, stress regulation, controlling of non-sexual motivated behavior, and sexual photoperiodicity in concert with other neuropeptides such as kisspeptin, neuropeptide-Y (NPY), pro-opiomelanocortin, orexin, and melanin. RFamide peptides synthesized in the granulosa cells, interstitial cells, and seminiferous tubule regulate steroidogenesis and gametogenesis in the gonads. The present review is intended to provide the recent findings that explore the role of RFRP-3 in regulating HPG axis and its potential applications in the synchronization of reproduction and its therapeutic interventions to prevent stress-induced amenorrhea.

Mannosylphosphodolichol synthase overexpression supports angiogenesis.

Mannosylphospho dolichol synthase (DPMS) plays a critical role in Glc(3)Man(9)GlcNAc(2)-PP-Dol (lipid-linked oligosaccharide, LLO) biosynthesis, an essential intermediate in asparagine-linked (N-linked) protein glycosylation. We have observed earlier that phosphorylation of DPMS increases the catalytic activity of the enzyme by increasing the V(max) as well as the enzyme turnover (k(cat)) without significantly changing the K(m) for GDP-mannose. As a result, LLO biosynthesis, turnover and protein N-glycosylation are increased. This is manifested in increased proliferation of capillary endothelial cells, i.e., angiogenesis. We have then asked if the phosphorylation event or the up-regulation of the DPMS due to over production of the enzyme is a key factor in up-regulating angiogenesis? This question has been answered by isolating a stable capillary endothelial cell clone overexpressing the DPMS gene. Our results indicate that the DPMS overexpressing clone has a high level DPMS mRNA judged by QRT-PCR. The clone also expresses nearly four-times higher DPMS protein over the clone transfected with pEGFP-N1 vector only (i.e., control) as analyzed by western blotting. Most importantly, the overexpressing DPMS clone has ~108% higher DPMS activity than that of the vector control. Immunofluorescence microscopy with Texas-Red conjugated WGA indicates a high level expression of GlcNAc-beta-(1,4)-GlcNAc)1-4-beta-GlcNAc-NeuAc glycans on the external surface of the capillary endothelial cells overexpressing DPMS. Increased cellular proliferation and accelerated healing of the wound induced by a mechanical stress of the DPMS overexpressing clone unequivocally supports DPMS for angiogenesis.