Bovine tuberculosis diagnosis is usually performed by various tests with specific limitations. Mycobacterium bovis culture filtrate contains antigenic proteins that could be used to improve the sensitivity of bovine tuberculosis diagnosis. The objective of this study was to identify and purify antigenic proteins from culture filtrates of M. bovis strain AN5 for use in immunological assays.

Forced polyploidization is an effective strategy for acute megakaryoblastic leukemia (AMKL) therapy and factors controlling polyploidization are potential targets for drug development. Although bone morphology protein 2-inducible kinase (BMP2K) has been implied to be a potential target for fasudil, a potent polyploidy-inducing compound, the function of BMP2K in megakaryopoiesis and AMKL remains unknown. This study aimed to investigate the role of BMP2K as a novel regulator in megakaryocyte polyploidization and differentiation and its implication in AMKL therapy.

More than half of the morbidity and mortality cases among children in Kenya are as a result of micronutrient deficiencies (MNDs). Food fortification is considered by the Government of Kenya as a feasible strategy for addressing MNDs. Worldwide, fortification has been proven to be effective since it does not require any change in dietary habits. Success of large-scale food fortification however may depend on consumer awareness of the fortification benefits. A cross-sectional study was conducted in 13 counties to collect information on fortification awareness using structured questionnaires. 1435 respondents were selected using the Lot Quality Assurance Sampling method. Data were analyzed using Stata version 14.0 and statistical significance p < 0.05. The study participants were described using descriptive statistics. The association of sociodemographic characteristics and awareness of fortification was performed using binary logistic regression analysis. The median age of the study participants was 35 years. Only 28% of the respondents were aware of the term "fortification." Of the respondents, about 27% heard of food fortification through radio. Vernacular radio emerged as the most preferred channel for communicating fortification information among 24.9% of the respondents. Although awareness of vitamins (32%) and minerals (1.5%) was limited, most (76%) respondents reported of existence of health risks for lacking micronutrients. Awareness of food fortification was significantly associated with respondents' occupation (p <  0.001), household size (p=0.012), education levels (p < 0.001), and age (p=0.025). There is need for a wider use of broadcast media sources to modify information and education materials to promote fortification awareness among Kenyan consumers.

The details of the immunological microenvironment and its clinical implications for pancreatic cancer are still unclear. In this study, we obtained data from public databases, such as the Gene Expression Omnibus, the Cancer Genome Atlas Program, the International Cancer Genome Consortium Data Portal, the ArrayExpress Data Warehouse, and the cBioPortal for Cancer Genomics. We used these data to evaluate the pattern of immune cells infiltration in pancreatic ductal adenocarcinoma (PDAC) tissues. We observed that the levels of M0 macrophages and activated dendritic cells in tumor tissues were significantly higher than that in para-tumor tissues. M0 macrophages, gamma delta T cells and naive CD4 T cells were independent predictive factors of a poor outcome for PDAC patients. An immune score determined by M0 macrophages, gamma delta T cells and naive CD4 T cells could predict the survival of patients. The results of this study suggest that the infiltration of immune cells, such as M0 macrophages, may be a possible target for the treatment of PDAC. However, these findings need to be confirmed by additional studies.

Breast cancer (BC) incidence is progressively increasing in Egypt. However, there is insufficient knowledge of the acquired somatic mutations in Egyptian BC patients which limit our understanding of its progression. To the best of our knowledge, this is the first Egyptian cohort to sequence a multiple-gene panel of cancer related genes on BC patients. Four hundred and nine cancer related genes were sequenced in 46 fresh breast tumors of Egyptian BC patients to identify somatic mutations and their frequencies. TP53 and PIK3CA were the most top two frequently mutated genes. We detected 15 different somatic mutations in TP53 and 8 different ones in PIK3CA, each in 27 samples (58.7%). According to Clinvar database; we found 19 pathogenic somatic mutations: 7 in Tp53, 5 in PIK3CA, and single variants of VHL, STK11, AKT1, KRAS, IDH2, PTEN and ERBB2. We also identified 5 variants with uncertain significance (4 in TP53 and 1 in CEBPA) and 4 variants with conflicting interpretations of pathogenicity (2 in TP53 and 1 in each of APC and JAK3). Moreover, one drug response variant (p.P72R) in TP53 was detected in 8 samples. Furthermore, four novel variants were identified in JAK2, MTOR, KIT and EPHB. Further analysis, by Ingenuity Variant Analysis software (IVA), showed that PI3K/AKT signaling is altered in greater than 50% of Egyptian BC patients which implicates PI3K/AKT signaling as a therapeutic target. In this cohort, we shed the light on the most frequently detected somatic mutations and the most altered pathway in Egyptian BC patients.

The objective of this systematic review is to critically evaluate the evidence of the effectiveness and safety of external application of herbal medicines (EAHM) for acne vurgalis (AV).

Unsatisfactory consequences of bone regeneration disorders in diabetes mellitus (DM) patients, their high prevalence, complication number, and difficulties in treatment require further study and deeper understanding of reparative osteogenesis mechanisms under chronic hyperglycemia and finding new effective and affordable approaches to their treatment. Therefore, the aim of our work was to study the histological, ultramicroscopic, and histomorphometric features of reparative osteogenesis in rats with chronic hyperglycemia (CH), as well as to investigate the possibility of platelet-rich plasma (PRP) use in a fracture area in order to correct the negative effects of CH on reparative osteogenesis processes. Study Object and Methods. The studies were performed on 70 white laboratory rats, mature males, which were divided into the following groups: control group, animals with posttraumatic tibial defect under conditions of CH exposure, rats with experimental CH that were administered with PRP into the bone defect, and animals for the assessment of glucose homeostasis and confirmation of simulated CH. Light microscopy was performed using an Olympus BH-2 microscope (Japan). Ultramicroscopic examination was performed using REM-102 scanning electron microscope. The statistical analysis was performed using SPSS-17 software package.

Monoacylglycerol lipase (MAGL) is a serine hydrolase that plays a crucial role catalysing the hydrolysis of monoglycerides into glycerol and fatty acids. It links the endocannabinoid and eicosanoid systems together by degradation of the abundant endocannabinoid 2-arachidaoylglycerol into arachidonic acid, the precursor of prostaglandins and other inflammatory mediators. MAGL inhibitors have been considered as important agents in many therapeutic fields, including anti-nociceptive, anxiolytic, anti-inflammatory, and even anti-cancer. Currently, ABX-1431, a first-in-class inhibitor of MAGL, is entering clinical phase 2 studies for neurological disorders and other diseases. This review summarizes the diverse (patho)physiological roles of MAGL and will provide an overview on the development of MAGL inhibitors. Although a large number of MAGL inhibitors have been reported, novel inhibitors are still required, particularly reversible ones.

Renal tubular epithelial cells (RTECs) are important target cells for the development of kidney-targeted drug delivery systems. Under physiological conditions, RTECs are under constant fluid shear stress (FSS) from original urine in the renal tubule and respond to changes of FSS by altering their morphology and receptor expression patterns, which may affect reabsorption and cellular uptake. Using a microfluidic system, controlled shear stress was applied to proximal tubule epithelial cell line HK-2. Next, 2-glucosamine, bovine serum albumin, and albumin nanoparticles were selected as representative carriers to perform cell uptake studies in HK-2 cells using the microfluidic platform system with controlled FSS. FSS is proven to impact the morphology of HK-2 cells and upregulate the levels of megalin and clathrin, which then led to enhanced cellular uptake efficiencies of energy-driven carrier systems such as macromolecular and albumin nanoparticles in HK-2 cells. To further investigate the effects of FSS on endocytic behavior mediated by related receptors, a mice model of acute kidney injury with reduced fluid shear stress was established. Consistent with in vitro findings, in vivo studies have also shown reduced fluid shear stress down-regulated the levels of megalin receptors, thereby reducing the renal distribution of albumin nanoparticles.

No abstract available

Haemolysis and methaemoglobinaemia (MetHb) are rare metabolic complications that can occur in Alkaptonuria (AKU), for which there is no curative treatment. Presented is a case of a man who had AKU, and serves as a reminder of life-threatening complications that can occur with haemolysis and MetHb. This case presents an opportunity to revisit important considerations relating to the investigation and treatment of haemolysis and MetHb with a view to raising awareness, and in doing so hopefully reducing the uniformly fatal outcome. Additionally it is proposed that treatment of haemolysis and MetHb with nitisinone is considered as a potentially lifesaving treatment as it is believed that reducing the concentration of circulating homogentisic acid will reduce oxidative stress.

Career development skills are widely advocated as part of research capacity building and strengthening efforts. However, there is a gap in knowledge on their acceptability in low- and middle-income countries.

Helicopters play an important role in trauma; however, this service comes with safety risks, high transport costs, and downstream care charges.

Thyroid storm (TS) is rare in pediatrics, most cases reported in literature responded well to medical therapy. We report the case of an adolescent female presented with TS refractory to anti-thyroid medical management. She had refractory hypertension, tachycardia, and progressive encephalopathy despite aggressive medical management. She underwent subtotal thyroidectomy after 2 weeks of failed medical management with a complete resolution of symptoms within days of surgery. We also learned sodium nitroprusside with its direct vasodilatory effect on conduit vessels, verapamil with its rate control properties, and labetalol with its dual sympathetic blockage property were beneficial in the management of this patient.

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal "microbiotypes" or "states": the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based on geography. We also describe a potential reciprocal relationship between Corynebacterium species and Staphylococcus aureus, suggesting that a certain microbial equilibrium between various players is reached in the sinuses. We validate our approach by applying it to a separate 16S rRNA gene sequence dataset of 97 sinus swabs from a different patient cohort. Sinonasal microbiotyping may prove useful in reducing the complexity of describing sinonasal microbiota. It may drive future studies aimed at modeling microbial interactions in the sinuses and in doing so may facilitate the development of a tailored patient-specific approach to the treatment of sinus disease in the future.

P63, and in particular the most expressed ΔNp63α isoform, seems to have a critical role in the outcome of head and neck cancer. Many studies have been conducted to assess the possible use of p63 as a prognostic marker in squamous cell carcinoma cancers, but the results are still not well-defined. Moreover, a clear relationship between the expression of ΔNp63α and the presence of high-risk HPV E6 and E7 oncoproteins has been delineated. Here we describe how ΔNp63α is mostly expressed in HPV-positive compared to HPV-negative head and neck cancer cell lines, with a very good correlation between ΔNp63α mRNA and protein levels.

The Methanosarcina mazei pyrrolysyl-tRNA synthetase (PylRS)⋅tRNAPyl pair can be used to incorporate non-canonical amino acids (ncAAs) into proteins at installed amber stop codons. Although engineering of the PylRS active site generates diverse binding pockets, the substrate ranges are found similar in charging lysine and phenylalanine analogs. To expand the diversity of the ncAA side chains that can be incorporated via the PylRS⋅tRNAPyl pair, exploring remote interactions beyond the active site is an emerging approach in expanding the genetic code research. In this work, remote interactions between tRNAPyl, the tRNA binding domain of PylRS, and/or an introduced non-structured linker between the N- and C-terminus of PylRS were studied. The substrate range of the PylRS⋅tRNAPyl pair was visualized by producing sfGFP-UAG gene products, which also indicated amber suppression efficiencies and substrate specificity. The unstructured loop linking the N-terminal and C-terminal domains (CTDs) of PylRS has been suggested to regulate the interaction between PylRS and tRNAPyl. In exploring the detailed role of the loop region, different lengths of the linker were inserted into the junction between the N-terminal and the C-terminal domains of PylRS to unearth the impact on remote effects. Our findings suggest that the insertion of a moderate-length linker tunes the interface between PylRS and tRNAPyl and subsequently leads to improved suppression efficiencies. The suppression activity and the substrate specificity of PylRS were altered by introducing three mutations at or near the N-terminal domain of PylRS (N-PylRS). Using a N-PylRS⋅tRNAPyl pair, three ncAA substrates, two S-benzyl cysteine and a histidine analog, were incorporated into the protein site specifically.

Objective: This study aims to investigate whether obstetric complications and perinatal outcomes after frozen embryo transfer (FET) in the programming cycles differ from that in the natural cycles. Methods: We conducted a retrospective cohort study collecting a total of 14,373 singletons born after frozen embryo transfer at the Center for Reproductive Medicine Affiliated to Shandong University from September 2013 to September 2018. The women were divided into two groups according to the regimens for endometrium preparation: either natural cycles (n = 10,211) or programming cycles (n = 4,162). The primary outcomes were the incidence of obstetric complications consisting of pre-eclampsia, gestational diabetes mellitus, placenta previa, placental abruption, and postpartum hemorrhage. The perinatal outcomes included average birthweight, low birthweight (LBW), very LBW, macrosomia, large for gestational age, and small for gestational age. Multivariable logistic regression analysis was performed to adjust for potential confounders. Results: The incidences of pre-eclampsia (8.6 vs. 3.8%) and postpartum hemorrhage (0.7 vs. 0.2%) in the programming FET cycles were significantly higher than those in the natural FET cycles. The logistic regression analysis showed that, compared to the natural FET cycles, the programming FET cycles were associated with an elevated risk of pre-eclampsia (aOR, 2.55; 95% CI, 2.06-3.16) and postpartum hemorrhage (aOR, 2.94; 95% CI, 1.44-5.99). Conclusion: The women with singleton delivery after frozen-thawed embryo transfer in the programming cycles had an elevated risk of pre-eclampsia and postpartum hemorrhage, which was speculated to be associated with the absence of the corpus luteum.

B7 homologue 6 (B7-H6), a newly identified member of the B7 costimulatory molecule family, is not only a crucial regulator of NK cell-mediated immune responses through binding to NKp30 but also has clinical implications due to its abnormal expression in human cancers. Here, we show that B7-H6 expression is abnormally upregulated in glioma tissue and that B7-H6 is coexpressed with stem cell marker Sox2. Intriguingly, B7-H6 was rarely detected on the surface of glioma cell lines but was abundantly expressed in glioma stem-like cells (GSLCs) that were derived from the glioma cell lines in vitro. Surprisingly, B7-H6 was the only one that was preferentially expressed in the GSLCs among the B7 family members. Functionally, knockdown of B7-H6 in GSLCs by siRNAs led to the inhibition of cell proliferation, with decrease in the expression of the oncogene Myc as well as inactivation of PI3K/Akt and ERK/MAPK signaling pathways. Moreover, we determined that three genes CBL (Casitas B-Lineage Lymphoma Proto-Oncogene), CCNT1 (Cyclin T1), and RNMT (RNA guanine-7 methyltransferase) were coexpressed with B7-H6 and c-myc in glioma tissue samples from the TCGA database and found, however that only RNMT expression was inhibited by the knockdown of B7-H6 expression in the GSLCs, suggesting the involvement of RNMT in the B7-H6/c-myc axis. Extending this to 293T cells, we observed that knocking out of B7-H6 with CRISPR-Cas9 system also suppressed cell proliferation. Thus, our findings suggest B7-H6 as a potential molecule for glioma stem cell targeted immunotherapy.

The immune response elicited by the protective whole-cell pertussis (wP) versus the less-protective acellular pertussis (aP) vaccine has been well characterized; however, important clinical problems remain unsolved, as the inability of the currently administered aP vaccine is resulting in the reemergence of clinical disease (i.e., whooping cough). Strong evidence has shown that original, childhood aP and wP priming vaccines provide a long-lasting imprint on the CD4+ T cells that impacts protective immunity. However, aP vaccination might prevent disease but not infection, which might also affect the breadth of responses to Bordetella pertussis (BP) antigens. Thus, characterizing and defining novel targets associated with T cell reactivity are of considerable interest. Here, we compare the T cell reactivity of original aP and wP priming for different antigens contained or not contained in the aP vaccine and define the basis of a full-scale genomic map of memory T cell reactivity to BP antigens in humans. Our data show that the original priming after birth with aP vaccines has higher T cell reactivity than originally expected against a variety of BP antigens and that the genome-wide mapping of BP using an ex vivo screening methodology is feasible, unbiased, and reproducible. This could provide invaluable knowledge towards the direction of a new and improved pertussis vaccine design.