The COPII-cargo adaptor complex Lst1-Sec23 selectively sorts proteins into vesicles that bud from the endoplasmic reticulum (ER) and traffic to the Golgi. Improperly folded proteins are prevented from exiting the ER and are degraded. ER-phagy is an autophagic degradation pathway that uses ER-resident receptors. Working in yeast, we found an unexpected role for Lst1-Sec23 in ER-phagy that was independent from its function in secretion. Up-regulation of the stress-inducible ER-phagy receptor Atg40 induced the association of Lst1-Sec23 with Atg40 at distinct ER domains to package ER into autophagosomes. Lst1-mediated ER-phagy played a vital role in maintaining cellular homeostasis by preventing the accumulation of an aggregation-prone protein in the ER. Lst1 function appears to be conserved because its mammalian homolog, SEC24C, was also required for ER-phagy.

Brucellosis is one of the most common contagious and communicable zoonotic diseases with high rates of morbidity and lifetime sterility. There has been a momentous increase over the recent years in intra/interspecific infection rates, due to poor management and limited resources, especially in developing countries. Abortion in the last trimester is a predominant sign, followed by reduced milk yield and high temperature in cattle, while in humans it is characterized by undulant fever, general malaise, and arthritis. While the clinical picture of brucellosis in humans and cattle is not clear and often misleading with the classical serological diagnosis, efforts have been made to overcome the limitations of current serological assays through the development of PCR-based diagnosis. Due to its complex nature, brucellosis remains a serious threat to public health and livestock in developing countries. In this review, we summarized the recent literature, significant advancements, and challenges in the treatment and vaccination against brucellosis, with a special focus on developing countries.

Key Points• IL-32 is a proinflammatory cytokine expressed by plasma cells in a subset of MM patients, and high expression correlates with poor survival.• IL-32 is induced by hypoxia and secreted from MM cells in EVs that promote bone destruction.

BackgroundCutaneous wound healing is a complex process involving several signaling pathways such as the Wnt and extracellular signal-regulated kinase (ERK) signaling pathways. Valproic acid (VPA) is a commonly used antiepileptic drug that acts on these signaling pathways; however, the effect of VPA on cutaneous wound healing is unknown.Methods and FindingsWe created full-thickness wounds on the backs of C3H mice and then applied VPA. After 7 d, we observed marked healing and reduced wound size in VPA-treated mice. In the neo-epidermis of the wounds, β-catenin and markers for keratinocyte terminal differentiation were increased after VPA treatment. In addition, α-smooth muscle actin (α-SMA), collagen I and collagen III in the wounds were significantly increased. VPA induced proliferation and suppressed apoptosis of cells in the wounds, as determined by Ki67 and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining analyses, respectively. In vitro, VPA enhanced the motility of HaCaT keratinocytes by activating Wnt/β-catenin, ERK and phosphatidylinositol 3-kinase (PI3-kinase)/Akt signaling pathways.ConclusionsVPA enhances cutaneous wound healing in a murine model and induces migration of HaCaT keratinocytes.

The Wnt/β-catenin pathway is a potential target for development of anabolic agents to treat osteoporosis because of its role in osteoblast differentiation and bone formation. However, there is no clinically available anti-osteoporosis drug that targets this Wnt/β-catenin pathway. In this study, we screened a library of aqueous extracts of 350 plants and identified Hovenia dulcis Thunb (HDT) extract as a Wnt/β-catenin pathway activator. HDT extract induced osteogenic differentiation of calvarial osteoblasts without cytotoxicity. In addition, HDT extract increased femoral bone mass without inducing significant weight changes in normal mice. In addition, thickness and area of femoral cortical bone were also significantly increased by the HDT extract. Methyl vanillate (MV), one of the ingredients in HDT, also activated the Wnt/β-catenin pathway and induced osteoblast differentiation in vitro. MV rescued trabecular or cortical femoral bone loss in the ovariectomized mice without inducing any significant weight changes or abnormality in liver tissue when administrated orally. Thus, natural HDT extract and its ingredient MV are potential anabolic agents for treating osteoporosis.

Background: Human brucellosis is a neglected and zoonotic disease also known as Malta fever or undulant fever. Objectives: A cross sectional study was conducted to determine the seroprevalence of brucellosis and to access the role of risk factors associated with this disease in humans of Punjab, Pakistan. Methods: A total of 250 serum samples were collected and subjected to Rose Bengal Plate Test and Enzyme Linked Immunosorbent Assay for screening of Brucella. A predesigned questionnaire was filled prior to sampling to collect data regarding socio -demographic and suspected risk factors of human brucellosis. Descriptive and bivariate statistical analysis was performed using the STATA software version 12. Results: The study showed 16% seroprevalence of brucellosis. The prevalence was statistically higher in males (24%), age group of 20 to 30 years (26.92%), rural residents, (23%) and individuals with animals at home (22.50%). Among the related risk factors, exposure to animals (OR = 1.87, 95% CI: 0.9459, 3.6973) and consuming raw milk (OR = 2.36, 95% CI: 1.1713, 4.7760) were strongly associated with the disease. Conclusions: Awareness programs in the rural population should be provided about the disease and its associated risk factors. Consuming unpasteurized milk and products should be avoided to control this disease.

In the current study; insecticidal, growth regulation, oviposition deterrence and repellency of petroleum ether extracts of Azadirachta indica, Penganum harmala, Datura stramonium, Tribulus terrestris and Chenopodium murale against 2nd instar larvae of housefly was investigated. Five different concentrations (5%, 10%, 15%, 20% and 25%) were used through larval feeding and the mortality data was recorded after 24, 48 and 72 hrs. Highest mortality was induced by P. harmala (63.87%) followed by D. stramonium (62.78%), A. indica (53.84%), T. terrestris (41.86%) and C. murale (4.09%) after 72 h at 25% concentration, respectively. Increased mortality was observed with increased time duration and concentration. Longest larval duration (9.33 ± 0.33 days) and pupal duration (7.33 ± 0.33 days) days) was recorded in larvae treated with 25% concentration of P. harmala which also caused a decrease in the activity of AChE, ACP, AKP, α-Carboxyl, and β-Carboxyl enzymes. However, at 25% concentration, C. murale showed highest oviposition deterrence activity (81.88%) followed by D. stramonium (79.58%). In comet assay test, at highest concentration (25%) the mean comet tail lengths represented by Penganum harmala, Datura stramonium and Azadirachta indica (Reference plant) were 10.20 ± 0.49, 9.20 ± 0.37 and 7.80 ± 0.49 μm while percent DNA damage was 10.56 ± 0.77, 10.67 ± 1.62 and 8.11 ± 0.85% respectively compared to controls cells. Phytochemical analysis indicated the presence of flavonoids, steroids, saponins, cardiac glycosides, tannins, alkaloids, terpenoids and anthraquinones. Fourier Transform Infrared spectroscopy (FTIR) analysis revealed the presence of phenolic flavonoids, saponins, tannins as major functional groups. Further studies are needed to explore and thus, to incorporate weed plant extracts for the management of house flies.

Secreted frizzled-related protein 4 (SFRP4) is a member of secreted protein family with sequence similarity to frizzled receptors of wingless-related integration site (Wnt) signaling pathways. These proteins control diverse functions from embryonic development to adults in many organisms including humans. Initially, SFRPs were recognized as antagonists of Wnt signaling and supposed to interact with Wnts. Further research demonstrated their interactions to frizzled receptors and a functional diversity was related to these proteins, Wnt signaling potentiation in addition to modulation. SFRP4 is the largest member of SFRP family and is implicated in many diseases including obesity, type 2 diabetes (T2D), and cancer. SFRP4 acts as a biomarker for T2D and was expressed several years before clinical diagnosis of disease. This review mainly focusses on the role of SFRP4 in obesity and how it can lead to β-cell failure and ultimately to T2D. The role of SFRP4 in adipose tissues causing increased production of adipokines lead to the oxidative stress in pancreas that particularly have low amount of antioxidant enzymes in pancreatic β-cells leading to failure in exocytosis of insulin containing granules causing T2D. Obesityinduced inflammation is a principal factor in pathogenesis of insulin resistance as well as metabolic syndrome. Pro-inflammatory cytokines have potential to cause insulin resistance in skeletal muscles, adipose tissue, and liver via inhibition of insulin signal transduction. Secretion of SFRP4 is mediated by interleukin 1-β (IL1-β). This review highlights the molecular mechanisms by which SFRP4 leads to T2D.Understanding of molecular mechanism and targeting SFRP4 could help to eradicate or reduce chances of developing T2D. K E Y W O R D S adipokines, obesity, SFRP4, type-2 diabetes, Wnt signaling 1 | INTRODUCTION Cellular activities and functions are coordinated through processing of biological information and communication between cells via different signaling molecules. These signaling molecules regulate gene expression in nucleus and in Abbreviations: C/EBP, CAAT/enhancer-binding protein; CRD, cystein rich domain; DKK, dickkopfs; FZD, frizzled receptors; IL, interleukin; LRP, low density lipoprotein receptor related protein; MCP1, monocyte chemotactic protein-1; MG, methylglyoxal; NLD, netrin-like domain; PKB, protein kinase B; Pparγ, peroxisome proliferator-activated receptor γ; SFRP4, secreted frizzled-related protein 4; T2D, type 2 diabetes; WIF, Wnt inhibitory factors; Wnt, wingless-related integration site.