Pharmacological targeting of gastric mucosal barrier with traditional Chinese medications for repairing gastric mucosal injury

Introduction: The gastric mucosa (GM) is the first barrier and vital interface in the stomach that protects the host from hydrochloric acid in gastric juice and defends against exogenous insults to gastric tissues. The use of traditional Chinese medications (TCMs) for the treatment of gastric mucosal injury (GMI) has long-standing history and a good curative effect. Whereas there are poor overall reports on the intrinsic mechanisms of these TCM preparations that pharmacology uses to protect body from GMI, which is crucial to treating this disease. These existing reviews have deficiencies that limit the clinical application and development of both customary prescriptions and new drugs.Methods: Further basic and translational studies must be done to elucidate the intrinsic mechanisms of influence of these TCM preparations. Moreover, well-designed and well-conducted experiences and clinical trials are necessary to ascertain the efficacy and mechanisms of these agents. Therefore, this paper presents a focused overview of currently published literature to assess how TCMs action that facilitates the cures for GMI. It offers a whole train of current state of pharmacological evidence, identifies the pharmacological mechanisms of TCMs on GM, and highlights that remarkable capacity of TCMs to restore GM after damage.Results: These TCMs preparations promote the repair of multicomponent targets such as the gastric mucus, epithelial layer, blood flow (GMBF) and lamina propria barrier.Summary: Overall, this study has summarized the essential regulatory mechanisms and pharmacological efficacy of TCMs on new and productive therapeutic targets.Discussion: This review provides an avenue for studying various drugs with potentially promising effects on mucosal integrity, as well as subsequent pharmacological studies, clinical applications, and new drug development

DDC-PIM: Efficient Algorithm/Architecture Co-design for Doubling Data Capacity of SRAM-based Processing-In-Memory

Processing-in-memory (PIM), as a novel computing paradigm, provides significant performance benefits from the aspect of effective data movement reduction. SRAM-based PIM has been demonstrated as one of the most promising candidates due to its endurance and compatibility. However, the integration density of SRAM-based PIM is much lower than other non-volatile memory-based ones, due to its inherent 6T structure for storing a single bit. Within comparable area constraints, SRAM-based PIM exhibits notably lower capacity. Thus, aiming to unleash its capacity potential, we propose DDC-PIM, an efficient algorithm/architecture co-design methodology that effectively doubles the equivalent data capacity. At the algorithmic level, we propose a filter-wise complementary correlation (FCC) algorithm to obtain a bitwise complementary pair. At the architecture level, we exploit the intrinsic cross-coupled structure of 6T SRAM to store the bitwise complementary pair in their complementary states ($Q/\overline{Q}$), thereby maximizing the data capacity of each SRAM cell. The dual-broadcast input structure and reconfigurable unit support both depthwise and pointwise convolution, adhering to the requirements of various neural networks. Evaluation results show that DDC-PIM yields about $2.84\times$ speedup on MobileNetV2 and $2.69\times$ on EfficientNet-B0 with negligible accuracy loss compared with PIM baseline implementation. Compared with state-of-the-art SRAM-based PIM macros, DDC-PIM achieves up to $8.41\times$ and $2.75\times$ improvement in weight density and area efficiency, respectively.Comment: 14 pages, to be published in IEEE Transactions on Computer-Aided Design of Integrated Circuits and Systems (TCAD

Clinical identification of expressed proteins in adrenal medullary hyperplasia detected with hypertension

BackgroundHypertension remains a challenging public health problem worldwide, and adrenal gland-related diseases are one class of the major causes for secondary hypertension. Among them, one relatively rare pattern is adrenal hyperplastic hypertension caused by adrenal medullary hyperplasia (AMH), leading to excessive secretion of autonomic catecholamine. Given that the pathological changes of adrenal medulla are not well correlated to the onset and even severity of secondary hypertension, the molecular basis why some AMH patients are accompanied with hypertension remains unclear and is worth exploring.AimsFor this reason, this study aims at investigating differentially expressed proteins in clinical AMH tissue, with special focus on the potential contribution of these differentially expressed proteins to AMH development, in order to have a better understanding of mechanisms how AMH leads to secondary hypertension to some extent.Methods and resultsTo this end, AMH specimens were successfully obtained and verified through computed tomography (CT) and haematoxylin-eosin (HE) staining. Proteomic analyses of AMH and control tissues revealed 782 kinds of differentially expressed proteins. Compared with the control tissue, there were 357 types of upregulated proteins and 425 types of downregulated proteins detected in AMH tissue. Of interest, these differentially expressed proteins were significantly enriched in 60 gene ontology terms (P < 0.05), including 28 biological process terms, 14 molecular function terms, and 18 cellular component terms. Pathway analysis further indicated that 306 proteins exert their functions in at least one Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. Western blotting showed enhanced expression of phenylethanolamine N- methyltransferase (PNMT), myelin protein zero (MPZ), and Ras-related protein Rab-3C (RAB3C), and reduced expression of cluster of differentiation 36 (CD36) observed in AMH tissue in comparison with controls.ConclusionsClinical AMH specimens display a different proteomic profile compared to control tissue. Of note, PNMT, MPZ, RAB3C, and CD36 are found to differentially expressed and can be potential targets for AMH, providing a theoretical basis for mechanistic exploration of AMH along with hypertension

Forensic psychiatric analysis of organic personality disorders after craniocerebral injury in Shanghai, China

ObjectiveTo explore the incidence rate and the differences of clinical manifestations of organic personality disorders with varying degrees of craniocerebral trauma.Materials and methodsAccording to the International Classification of Diseases-10, 1,027 subjects with craniocerebral trauma caused by traffic accidents were reviewed, the degrees of craniocerebral trauma were graded and those with personality disorder after craniocerebral trauma were diagnosed. The personality characteristics of all patients were evaluated by using the simplified Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI).ResultsThe incidence rate of organic personality disorder after all kinds of craniocerebral trauma was 33.1%, while it was 38.7 and 44.2% in the patients after moderate and severe craniocerebral trauma, respectively, which was significantly higher than that in the patients after mild craniocerebral trauma (18.0%) (P < 0.05). Compared with the patients without personality disorder, the neuroticism, extraversion and agreeableness scores all showed significantly differences (P < 0.05) in the patients with personality disorder after craniocerebral trauma; especially the conscientiousness scores showed significant differences (P < 0.05) in the patients with personality disorder after moderate and severe craniocerebral trauma. The agreeableness and conscientiousness scores in the patients with personality disorder after moderate and severe craniocerebral trauma were significantly lower than that after mild craniocerebral trauma, and the patients with personality disorder after severe craniocerebral trauma had lower scores in extraversion than that after mild craniocerebral trauma.ConclusionThe severity and area of craniocerebral trauma is closely related to the incidence rate of organic personality disorder, and it also affects the clinical manifestations of the latter, which provides a certain significance and help for forensic psychiatric appraisal

Transcriptional profiles of different states of cancer stem cells in triple-negative breast cancer

Abstract Breast cancer stem cells (BCSCs) are thought to be responsible for tumor initiation, metastasis and relapse. Our group and others have described markers useful in isolating BCSCs just as aldehyde dehydrogenase positive (ALDH+) or CD24−CD44+. In fact, cells which simultaneously express both sets of markers have the highest tumor initiating capacity. Although the transcriptomic profile of cells expressing each BCSC marker alone has been reported, the profile of the most tumorigenic population expressing both sets of markers has not. Here we used the biomarker combination of ALDH and CD24/CD44 to sort four populations isolated from triple-negative breast cancer (TNBC) patient-derived xenografts, and performed whole-transcriptome sequencing on each population. We systematically compared the profiles of the three states of BCSCs (ALDH+CD24−CD44+, ALDH+non-CD24−CD44+ and ALDH−CD24−CD44+) to that of the differentiated tumor cells (ALDH−non-CD24−CD44+). For the first time, we compared the ALDH+CD24−CD44+ BCSCs with the other two BCSC populations. In ALDH+CD24−CD44+ BCSCs, we identified P4HA2, PTGR1 and RAB40B as potential prognostic markers, which were virtually related to the status of BCSCs and tumor growth in TNBC cells.https://deepblue.lib.umich.edu/bitstream/2027.42/142395/1/12943_2018_Article_809.pd

Tandem-Mass-Tag based proteomic analysis facilitates analyzing critical factors of porous silicon nanoparticles in determining their biological responses under diseased condition

The analysis of nanoparticles' biocompatibility and immunogenicity is mostly performed under a healthy condition. However, more clinically relevant evaluation conducted under pathological condition is less known. Here, the immunogenicity and bio-nano interactions of porous silicon nanoparticles (PSi NPs) are evaluated in an acute liver inflammation mice model. Interestingly, a new mechanism in which PSi NPs can remit the hepatocellular damage and inflammation activation in a surface dependent manner through protein corona formation, which perturbs the inflammation by capturing the pro-inflammatory signaling proteins that are inordinately excreted or exposed under pathological condition, is found. This signal sequestration further attenuates the nuclear factor kappa B pathway activation and cytokines production from macrophages. Hence, the study proposes a potential mechanism for elucidating the altered immunogenicity of nanomaterials under pathological conditions, which might further offer insights to establish harmonized standards for assessing the biosafety of biomaterials in a disease-specific or personalized manner.Peer reviewe

Production of Transgenic Pigs with an Introduced Missense Mutation of the Bone Morphogenetic Protein Receptor Type IB Gene Related to Prolificacy

In the last few decades, transgenic animal technology has witnessed an increasingly wide application in animal breeding. Reproductive traits are economically important to the pig industry. It has been shown that the bone morphogenetic protein receptor type IB (BMPR1B) A746G polymorphism is responsible for the fertility in sheep. However, this causal mutation exits exclusively in sheep and goat. In this study, we attempted to create transgenic pigs by introducing this mutation with the aim to improve reproductive traits in pigs. We successfully constructed a vector containing porcine BMPR1B coding sequence (CDS) with the mutant G allele of A746G mutation. In total, we obtained 24 cloned male piglets using handmade cloning (HMC) technique, and 12 individuals survived till maturation. A set of polymerase chain reactions indicated that 11 of 12 matured boars were transgene-positive individuals, and that the transgenic vector was most likely disrupted during cloning. Of 11 positive pigs, one (No. 11) lost a part of the terminator region but had the intact promoter and the CDS regions. cDNA sequencing showed that the introduced allele (746G) was expressed in multiple tissues of transgene-positive offspring of No.11. Western blot analysis revealed that BMPR1B protein expression in multiple tissues of transgene-positive F1 piglets was 0.5 to 2-fold higher than that in the transgene-negative siblings. The No. 11 boar showed normal litter size performance as normal pigs from the same breed. Transgene-positive F1 boars produced by No. 11 had higher semen volume, sperm concentration and total sperm per ejaculate than the negative siblings, although the differences did not reached statistical significance. Transgene-positive F1 sows had similar litter size performance to the negative siblings, and more data are needed to adequately assess the litter size performance. In conclusion, we obtained 24 cloned transgenic pigs with the modified porcine BMPR1B CDS using HMC. cDNA sequencing and western blot indicated that the exogenous BMPR1B CDS was successfully expressed in host pigs. The transgenic pigs showed normal litter size performance. However, no significant differences in litter size were found between transgene-positive and negative sows. Our study provides new insight into producing cloned transgenic livestock related to reproductive traits

A Novel Strategy to Screen Bacillus Calmette-Guérin Protein Antigen Recognized by γδ TCR

BACKGROUND: Phosphoantigen was originally identified as the main γδ TCR-recognized antigen that could activate γδ T cells to promote immune protection against mycobacterial infection. However, new evidence shows that the γδ T cells activated by phosphoantigen can only provide partial immune protection against mycobacterial infection. In contrast, whole lysates of Mycobacterium could activate immune protection more potently, implying that other γδ TCR-recognized antigens that elicit protective immune responses. To date, only a few distinct mycobacterial antigens recognized by the γδ TCR have been characterized. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we established a new approach to screen epitopes or protein antigens recognized by the γδ TCR using Bacillus Calmette-Guérin- (BCG-) specific γ TCR transfected cells as probes to pan a 12-mer random-peptide phage-displayed library. Through binding assays and functional analysis, we identified a peptide (BP3) that not only binds to the BCG-specific γδ TCR but also effectively activates γδ T cells isolated from human subjects inoculated with BCG. Importantly, the γδ T cells activated by peptide BP3 had a cytotoxic effect on THP-1 cells infected with BCG. Moreover, the oxidative stress response regulatory protein (OXYS), a BCG protein that matches perfectly with peptide BP3 according to bioinformatics analysis, was confirmed as a ligand for the γδ TCR and was found to activate γδ T cells from human subjects inoculated with BCG. CONCLUSIONS/SIGNIFICANCE: In conclusion, our study provides a novel strategy to identify epitopes or protein antigens for the γδ TCR, and provides a potential means to screen mycobacterial vaccines or candidates for adjuvant