ResearchPad - Pharmacology https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Challenges and Future Prospects of Precision Medicine in Psychiatry]]> https://www.researchpad.co/product?articleinfo=Nc7e14344-465a-4b7b-bbc3-e5736a6e7375

Abstract

Precision medicine is increasingly recognized as a promising approach to improve disease treatment, taking into consideration the individual clinical and biological characteristics shared by specific subgroups of patients. In specific fields such as oncology and hematology, precision medicine has already started to be implemented in the clinical setting and molecular testing is routinely used to select treatments with higher efficacy and reduced adverse effects. The application of precision medicine in psychiatry is still in its early phases. However, there are already examples of predictive models based on clinical data or combinations of clinical, neuroimaging and biological data. While the power of single clinical predictors would remain inadequate if analyzed only with traditional statistical approaches, these predictors are now increasingly used to impute machine learning models that can have adequate accuracy even in the presence of relatively small sample size. These models have started to be applied to disentangle relevant clinical questions that could lead to a more effective management of psychiatric disorders, such as prediction of response to the mood stabilizer lithium, resistance to antidepressants in major depressive disorder or stratification of the risk and outcome prediction in schizophrenia. In this narrative review, we summarized the most important findings in precision medicine in psychiatry based on studies that constructed machine learning models using clinical, neuroimaging and/or biological data. Limitations and barriers to the implementation of precision psychiatry in the clinical setting, as well as possible solutions and future perspectives, will be presented.

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<![CDATA[Gallic Acid Impedes Non-Small Cell Lung Cancer Progression via Suppression of EGFR-Dependent CARM1-PELP1 Complex]]> https://www.researchpad.co/product?articleinfo=N1b23bc24-670a-43db-a66c-d8a2ae305fb9

Background

Non-small cell lung cancer (NSCLC) is a common cause of cancer-related deaths. This study identified the regulatory pattern of gallic acid in NSCLC.

Methods

Human NSCLC cells were treated with different doses of gallic acid, after which, MTT assay and flow cytometry were performed to determine the survival and apoptotic rate of human NSCLC cells. Then, co-immunoprecipitation assay was performed to analyze the relationships between gallic acid, epidermal growth factor receptor (EGFR), and CARM1-PELP1. Next, we analyzed whether PELP1, CARM1 and EGFR were associated with the effects of gallic acid on NSCLC cells by conducting rescue experiments. The expression pattern of phosphorylated EGFR, EGFR, Ki67, as well as Fas, FasL and Caspase 3 proteins in cancer cells or xenografts was measured by Western blot analysis. Lastly, the role of gallic acid in the tumor growth was assessed in nude mice.

Results

The ideal dose of gallic acid that presented good suppressive effect on NSCLC cells were 30 μM, 50 μM and 75 μM, respectively. Gallic acid played an inhibiting role in the activation of EGFR, which further reduced the formation of CARM1-PELP1 complex, ultimately repressed the proliferation and elevated apoptosis of NSCLC cells. Meanwhile, CARM1 repression led to decreased growth, proliferation and migration abilities of NSCLC cells. Animal experiments confirmed that gallic acid contributed to the inhibition of tumor growth in vivo.

Conclusion

To sum up, gallic acid could potentially prevent NSCLC progression via inhibition of EGFR activation and impairment of the binding of CARM1 to PELP1, highlighting a novel therapy to dampen NSCLC progression.

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<![CDATA[Discovery of Potential Plasma Biomarkers for Tuberculosis in HIV-Infected Patients by Data-Independent Acquisition-Based Quantitative Proteomics]]> https://www.researchpad.co/product?articleinfo=Nfa5d7b87-9f00-4610-a582-184e25b54d5c

Purpose

Tuberculosis (TB) is the leading cause of mortality in individuals infected with human immunodeficiency virus (HIV), yet the methods for detecting Mycobacterium tuberculosis at an early stage remain insensitive or ineffective. This study aimed to discover plasma biomarkers for distinguishing HIV-TB coinfected individuals from HIV individuals without TB (HIV-nonTB).

Patients and Methods

A total of 200 Chinese HIV-positive patients were recruited, 100 each for HIV-nonTB group and HIV-TB group. Plasma proteomic profiles were analyzed for 50 patients each in both groups, using data-independent acquisition (DIA)-mass spectrometry-based proteomics. Differently expressed proteins were revealed with ridge regression analysis. Enzyme-linked immunosorbent assay (ELISA) analyses were performed for further validation in other 100 patients.

Results

DIA-mass spectrometry revealed 13 upregulated and 33 downregulated proteins in the HIV-TB group. AMACR (α-methylacyl-CoA racemase), LDHB (L-lactate dehydrogenase B chain), and RAP1B (Ras-related protein Rap-1b) were selected for building a diagnostic model, for which the receiver operation characteristic curve had under areas of 0.99 and 0.89 testing with proteomics data (sensitivity = 92%, specificity = 100%) and ELISA data (sensitivity = 76%, specificity = 92%), respectively.

Conclusion

The combination of AMACR, LDHB, and RAP1B proteins may serve as a potential marker of TB in HIV-infected patients.

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<![CDATA[ACAT2 Promotes Cell Proliferation and Associates with Malignant Progression in Colorectal Cancer]]> https://www.researchpad.co/product?articleinfo=Nd0c065e5-85fa-40b2-a9c5-f323541897cd

Background and Aims

Colorectal cancer (CRC) is a major disease that threatens human health. It has been reported that the acyl-coenzyme A (CoA): cholesterol acyltransferase 2 (ACAT2) gene can promote the progression of hepatocellular carcinoma, but its function in CRC is still unclear. In this study, we aimed to elucidate the function of ACAT2 in CRC.

Methods

Western blot and qPCR were used to detect the relative level of ACAT2 in CRC tissue and adjacent non-cancerous tissues, and then the association between ACAT2 expression and the clinicopathological features and survival of CRC patients were assessed. The expression of ACAT2 in CT26 and DLD1 cells was down-regulated by siRNA, and the effects of ACAT2 knockdown on cell proliferation were examined. The inhibitory effects of ACAT2 knockdown were further confirmed by tumor growth assays in vivo.

Results

Our data showed that the expression of ACAT2 in CRC tissues was markedly higher than in adjacent non-cancerous tissues. The high expression of ACAT2 was significantly associated with tumor size, lymph node metastasis and clinical stage. The increased expression of ACAT2 was also significantly associated with worse 5-year overall survival of CRC patients. siRNA-mediated ACAT2 knockdown strongly inhibited CT26 and DLD1 cells proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in these cells. Knockdown of ACAT2 expression suppressed the growth of CRC and inhibited the expression of Ki67 in vivo.

Conclusion

Our study demonstrated that ACAT2 played a positive role in regulating the proliferation of CRC and may be useful as a potential biomarker and therapeutic target for this disease.

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<![CDATA[Mitofusin1 Is a Major Mediator in Glucose-Induced Epithelial-to-Mesenchymal Transition in Lung Adenocarcinoma Cells]]> https://www.researchpad.co/product?articleinfo=N740baced-cc25-4460-acf8-d6e46745ed29

Background

Epithelial-to-mesenchymal transition (EMT) has been considered a latent mediator of diverse biological processes in cancer. However, the mechanisms involved in high glucose-associated EMT in lung adenocarcinoma (LAD) have not been fully clarified. In this study, we aimed to investigate whether mitofusin1 (MFN1) is involved in the EMT of LAD cells induced by glucose and to identify the molecular mechanism involved in this process.

Materials and Methods

The expression of specific proteins was analysed by Western blotting, immunohistochemistry, co-immunoprecipitation and immunofluorescence analysis. The proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8, bromodeoxyuridine incorporation, wound-healing and transwell assays. Lung tissues of adjacent normal regions and lung tissues from patients with LAD and LAD combined with diabetes mellitus were collected to determine the expression and significance of MFN1.

Results

Here, we showed that the expression of MFN1 was increased in LAD tissues compared with adjacent normal tissues and expression was even higher in lung tissues from patients with LAD combined with diabetes. In the lung cancer cell line A549, increased cell proliferation, invasion and EMT induced by high glucose were inhibited by MFN1 silencing. Mechanistic studies demonstrated that inhibiting autophagy reversed the abnormal EMT triggered by high glucose conditions. In addition, our data provide novel evidence demonstrating that PTEN-induced kinase (Pink) is a potential regulator involved in MFN1-mediated cell autophagy, which eventually leads to high glucose-induced proliferation, invasion and EMT of A549 cells.

Conclusion

Taken together, our data show that MFN1 interacts with Pink to induce the autophagic process and that the abnormal occurrence of autophagy ultimately contributes to glucose-induced pathological EMT in LAD.

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<![CDATA[High Serum Neuron-Specific Enolase Level Is Associated with Mild Cognitive Impairment in Patients with Diabetic Retinopathy]]> https://www.researchpad.co/product?articleinfo=N3bedff73-70e0-40e1-9672-8f56c1c90a99

Purpose

Diabetic retinopathy (DR) can increase the risk of mild cognitive impairment (MCI), which has been confirmed by previous researches. With the frequent occurrence of MCI in patients with DR, the early detection of MCI has become a research hot-spot. The aim of this study was to investigate the relationship between neuron-specific enolase (NSE) and MCI in patients with DR.

Patients and Methods

A total of 124 patients with DR, including 56 MCI patients and 68 normal cognition patients, were recruited in this cross-sectional study. The demographic and clinical data of patients were collected through questionnaires. Serum NSE was measured using electrochemiluminescence immunoassay. The Minimum Mental State Examination (MMSE) scale was used to evaluate the cognitive function of the participants.

Results

Compared with the normal cognition group, serum NSE levels and HbA1c levels in the MCI group were higher, while MMSE scores and educational level were lower (P<0.05). Serum NSE levels were significantly negatively correlated with MMSE total score, attention and calculation score, and language score (P<0.05). After adjusting for confounding factors, serum NSE still increased the MCI risk in DR patients (OR:1.606, 95CI%:1.264–2.041, P<0.001). The areas under the receiver operating characteristics (ROC) curves (AUC) of the crude model and the adjusted model were 0.75 and 0.73, respectively.

Conclusion

A high serum NSE level is an independent risk factor for MCI in DR patients. In addition, serum NSE is expected to be a potential biomarker in DR patients with MCI.

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<![CDATA[Dihydroartemisinin Prevents Progression and Metastasis of Head and Neck Squamous Cell Carcinoma by Inhibiting Polarization of Macrophages in Tumor Microenvironment]]> https://www.researchpad.co/product?articleinfo=N2711109f-0f80-479f-aff7-72b2658f3ed0

Background

Polarized M2 macrophages are an important type of tumor-associated macrophage (TAM), with roles in the growth, invasion, and migration of cancer cells in the tumor microenvironment. Dihydroartemisinin (DHA), a traditional Chinese medicine extract, has been shown to inhibit the progression and metastasis of head and neck squamous cell carcinoma (HNSCC); however, the effect of DHA on cancer prevention, and the associated mechanism, has not been investigated in the tumor microenvironment.

Materials and Methods

First, human Thp-1 monocytes were induced and differentiated into M2 macrophages using phorbol 12-myristate 13-acetate (PMA), interleukin-6 (IL-6), and interleukin-4 (IL-4). Induction success was confirmed by cell morphology evaluation, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). Then, DHA was applied to interfere with M2 macrophage polarization, and conditioned medium (CM), including conditioned medium from M2 macrophages (M2-CM) and conditioned medium from M2 macrophages with DHA (M2-DHA-CM), was obtained. CM was applied to Fadu or Cal-27 cells, and its effects on cancer invasion, migration, and angiogenesis were evaluated using transwell, wound-healing, and tube formation assays, respectively. Finally, Western blotting was used to evaluate the relationship between signal transducer and activator of transcription 3 (STAT3) signaling pathway activation and M2 macrophage polarization.

Results

Human Thp-1 monocytes were successfully polarized into M2-like TAMs using PMA, IL-6, and IL-4. We found that M2-like TAMs promoted the invasion, migration, and angiogenesis of HNSCC cells; however, DHA significantly inhibited IL-4/IL-6-induced M2 macrophage polarization. Additionally, as DHA induced a decrease in the number of M2-like TAMs, M2-DHA-CM inhibited the induction of invasion, migration, and angiogenesis of Fadu and Cal-27 cells. Finally, DHA inhibited M2 macrophage polarization by blocking STAT3 pathway activation in macrophages.

Conclusion

DHA inhibits the invasion, migration, and angiogenesis of HNSCC by preventing M2 macrophage polarization via blocking STAT3 phosphorylation.

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<![CDATA[The Parkinson’s Disease Death Rate: Carbidopa and Vitamin B6 [Expression of Concern]]]> https://www.researchpad.co/product?articleinfo=N7c6defb2-2a43-4d91-bfde-27abec93ac10 ]]> <![CDATA[In vitro Multistage Malaria Transmission Blocking Activity of Selected Malaria Box Compounds]]> https://www.researchpad.co/product?articleinfo=N33dbfc47-3e99-40b1-8df9-cdee7f2bea3a

Purpose

Continuous efforts into the discovery and development of new antimalarials are required to face the emerging resistance of the parasite to available treatments. Thus, new effective drugs, ideally able to inhibit the Plasmodium life-cycle stages that cause the disease as well as those responsible for its transmission, are needed. Eight compounds from the Medicines for Malaria Venture (MMV) Malaria Box, potentially interfering with the parasite polyamine biosynthesis were selected and assessed in vitro for activity against malaria transmissible stages, namely mature gametocytes and early sporogonic stages.

Methods

Compound activity against asexual blood stages of chloroquine-sensitive 3D7 and chloroquine-resistant W2 strains of Plasmodium falciparum was tested measuring the parasite lactate dehydrogenase activity. The gametocytocidal effect was determined against the P. falciparum 3D7elo1-pfs16-CBG99 strain with a luminescent method. The murine P. berghei CTRP.GFP strain was employed to assess compounds activities against early sporogonic stage development in an in vitro assay simulating mosquito midgut conditions.

Results

Among the eight tested molecules, MMV000642, MMV000662 and MMV006429, containing a 1,2,3,4-tetrahydroisoquinoline-4-carboxamide chemical skeleton substituted at N-2, C-3 and C-4, displayed multi-stage activity. Activity against asexual blood stages of both strains was confirmed with values of IC50 (50% inhibitory concentration) in the range of 0.07–0.13 µM. They were also active against mature stage V gametocytes with IC50 values below 5 µM (range: 3.43–4.42 µM). These molecules exhibited moderate effects on early sporogonic stage development, displaying IC50 values between 20 and 40 µM.

Conclusion

Given the multi-stage, transmission-blocking profiles of MMV000642, MMV000662, MMV006429, and their chemical characteristics, these compounds can be considered worthy for further optimisation toward a TCP5 or TCP6 target product profile proposed by MMV for transmission-blocking antimalarials.

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<![CDATA[An Oncolytic Vaccinia Virus Armed with GM-CSF and IL-24 Double Genes for Cancer Targeted Therapy]]> https://www.researchpad.co/product?articleinfo=Nb48b35f5-1f83-4ab9-9c0f-23e96a7d6974

Purpose

Targeted oncolytic vaccinia virus is an attractive candidate for cancer therapy due to its replication causing lysis of infected tumor cells as well as a delivery vector to overexpress therapeutic transgenes. This study constructed a novel oncolytic vaccinia virus carrying granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-24 (IL-24) double genes to improve efficacy for cancer therapy.

Methods

Vaccinia virus co-expressing GM-CSF and IL-24 based on Chinese Guang9 strain (VG9-GMCSF-IL24) was constructed with disruption of the viral thymidine kinase (TK) gene. The cytotoxicity of VG9-GMCSF-IL24 in various cell lines was assessed by MTT. The synergistic antitumor effect of VG9-GMCSF-IL24 in vivo was assessed on multiple tumor models.

Results

In vitro cytotoxicity assay showed that VG9-GMCSF-IL24 exerted a strongly cytotoxic effect on cancer cells, but with no significant cytotoxicity to normal cells. Significant tumor growth inhibition and prolonged survival were observed in different tumor models treated with VG9-GMCSF-IL24. Additionally, systemic and specific antitumoral immunity was investigated in vivo, and enhanced antitumor immunity was observed in VG9-GMCSF-IL24-treated mice.

Conclusion

Our results indicated that VG9-mediated GM-CSF and IL-24 co-expression performed cooperative and overlapping antitumor effect. As a novel and effective therapeutic strategy for cancer, the combination of oncolysis and immunotherapy with vaccinia virus carrying one or more immunostimulatory genes may have a satisfactory clinical application prospect.

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<![CDATA[Association Between Blood Glucose Within 24 Hours After Intensive Care Unit Admission and Prognosis: A Retrospective Cohort Study]]> https://www.researchpad.co/product?articleinfo=Nf0df6fc6-6927-46bb-bccc-b03c0110e224

Purpose

The aim of this study was to evaluate the association between blood glucose within 24 hours after intensive care unit (ICU) admission and prognosis.

Patients and Methods

A retrospective cohort study was conducted using data from a large critical care database. Patients who had a length of ICU stay ≥24 hours and at least two blood glucose records within 24 hours after ICU admission were included and hospital mortality was chosen as the primary outcome. The average, minimum, and maximum blood glucose within 24 hours after ICU admission were a priori selected as exposures and associations between each exposure and outcomes were assessed after adjusted for potential confounders.

Results

A total of 14,237 patients were included finally with an average age of 62.9±17.7 years and a mean SAPS II on admission of 34 (26–44). Among the study population, 20.2% (2872/14,237) had uncomplicated diabetes, and 6.7% (953/14,237) had complicated diabetes. Lowest hospital mortality rate was observed in the stratum with an average blood glucose ranged 110–140 mg/dL, a minimum blood glucose ranged 80–110 mg/dL, and a maximum blood glucose ranged 110–140 mg/dL. After adjusted for confounders including age, sex, disease severity scores and comorbidities, an average blood glucose ranged 110–140 mg/dL, a minimum blood glucose ranged 80–110 mg/dL, and a maximum blood glucose ranged 110–140 mg/dL were associated with the lowest risk of hospital mortality. Consistent results were found among patients without diabetes in the subgroup analyses stratified by diabetes.

Conclusion

A range of 110–140 mg/dL for average and maximum blood glucose and a range of 80–110 mg/dL for minimum blood glucose within 24 hours after ICU admission predicted better prognosis especially among patients without diabetes.

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<![CDATA[Association Between Metabolic Syndrome and Its Components with Severity of Acute Pancreatitis]]> https://www.researchpad.co/product?articleinfo=Nc72007ca-839d-4b51-b527-6c6eabbd1838

Background

Acute pancreatitis (AP) and metabolic syndrome (MetS) are common clinical problems with serious complications and high cost of treatment. The relationship between MetS and severity of AP is unknown, and because there are very few published articles, further studies had been recommended. Therefore, we designed this study to estimate the association between MetS and its components with AP severity.

Patients and Methods

In this prospective analytical cross-sectional study, all AP patients who referred to two referral hospitals affiliated with Shiraz University of Medical Sciences between 2016 and 2019 were evaluated. The diagnosis of MetS syndrome as well as follow-up of patients for evaluation of severity and outcome of AP was performed in all enrolled patients. National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP-III) was used for diagnosis of MetS. Bedside Index for Severity in Acute Pancreatitis (BISAP) and revised Atlanta classification (RAC) were used to estimate the severity of AP. Finally, the association between MetS syndrome and its components at different AP severities was compared.

Results

Of the 214 patients referred to our center, a total of 76 patients with AP were included in this study. Of the included patients, 40 (52.6%) were male and 36 (47.4%) were female. Frequency of patients in Mets and non-MetS groups was 34 (44.74%) and 42 (55.26%), respectively. The gender and mean age difference between Mets and non-MetS groups were not statistically significant. According to Mets groups, 25 (73.5%) and 9 (26.5%) AP patients with MetS had BISAP score of 0–2 and 3–5, respectively. BISAP score in MetS group was significantly higher than non-MetS group (P = 0.022). Overall, 20 (58.8%), 11 (32.4%), and 3 (8.8%) of AP patients with MetS had mild, moderately severe, and severe AP based on RAC, respectively. Severe RAC was significantly higher in the MetS group than in the non-MetS group (P = 0.029). The frequency of complications in MetS group was significantly higher than in non-MetS group (P= 0.008). The length of hospital stay was also significantly higher in the MetS group than in the non-MetS group (P = 0.001). Overall, three patients died, two of whom had MetS and all had severe RAC and BISAP 3–5. Waist circumference, fasting blood sugar, and triglyceride were significantly higher in the severe and moderately severe types of AP group than in the mild AP group, according to RAC. Although, mean of all components of MetS except HDL-cholesterol were higher in BISAP of 3–5 group than BISAP of 0–2 group, the difference was only significant in waist circumference.

Conclusion

The present study showed that there was a significant association between the rate of MetS and its components including waist circumference, hyperglycemia and hypertriglyceridemia with increasing AP severity. This study showed that the incidence of more severe AP in patients with MetS is much higher than in patients without MetS. We recommend that the new studies with larger sample sizes are conducted with careful consideration of confounding factors to investigate the relationship between the severity of MetS and AP as well as the effect of MetS treatment on the nature of AP.

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<![CDATA[Genomic and Phenotypic Diversity of Listeria monocytogenes Causing Pregnancy-Associated Listeriosis from Zhejiang Province, China, 2016–2018]]> https://www.researchpad.co/product?articleinfo=Nd50c7e99-53bc-478b-a9bc-d840a2e290a5

Introduction

There are few investigations describing the pregnancy-associated listeriosis in China, and the molecular characteristics of Listeria monocytogenes causing such infections remain largely unknown. We aim to investigate the phenotypic and genomic profiles of pregnancy-associated L. monocytogenes isolates and their association with isolates recovered from human and non-human in China.

Materials and Methods

In this study, we conducted a 3-year surveillance of listeriosis in a women’s hospital in Zhejiang province, using whole genome sequencing and bioinformatics tools.

Results

From 2016 to 2018, we identified 13 clinical L. monocytogenes isolates. Among these pregnancy-associated isolates, we found seven sequence types (STs), with the prevalent STs of ST87 and ST7. Serotyping divided the strains into four serotypes, including serotype 1/2a, 1/2b, 3a, and 4b. Antimicrobial resistance testing showed that all the isolates were susceptible to 10 antibiotics. Comparative genomics analysis clearly classified our genome collection into four distinct evolutionary lineages with most isolates grouping into lineages I and II. Interestingly, we found three pairs of isolates with high identity, although no evident epidemiological association was observed.

Conclusion

This study reports for the first time the surveillance of pregnancy-associated listeriosis in Zhejiang province, China, which indicates that the infection rate is low in this region. Our findings provide insight into the evolution and genetic diversity of pregnancy-associated L. monocytogenes from Zhejiang province. Additional investigations involving more human and non-human isolates with a “one health” strategy are needed for prediction of the listeriosis risk associated with a typical prevalent clone in Zhejiang province, such as ST87.

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<![CDATA[The Role of JNk Signaling Pathway in Obesity-Driven Insulin Resistance]]> https://www.researchpad.co/product?articleinfo=N30a740e4-87eb-44f7-b49e-b6326a0aaed7

Abstract

Obesity is not only closely related to insulin resistance but is one of the main factors leading to the formation of Type 2 Diabetes (T2D) too. The c-Jun N-terminal kinase (JNK) family is a member of the mitogen-activated protein kinase (MAPK) superfamily. JNK is also one of the most investigated signal transducers in obesity and insulin resistance. JNK-centric JNK signaling pathway can be activated by growth factors, cytokines, stress responses, and other factors. Many researches have identified that the activated phosphorylation JNK negatively regulates insulin signaling pathway in insulin resistance which can be simultaneously regulated by multiple signaling pathways related to the JNK signaling pathway. In this review, we provide an overview of the composition of the JNK signaling pathway, its regulation of insulin signaling pathway, and the relationship between the JNK signaling pathway and other pathways in insulin resistance.

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<![CDATA[Effects of Two Types of Moderate- and High-Intensity Interval Training on Serum Salusin-α and Salusin-β Levels and Lipid Profile in Women with Overweight/Obesity]]> https://www.researchpad.co/product?articleinfo=Nf778aaf6-195d-4f03-b861-c3f1b693934d

Objective

The current study aimed to compare the effects of two modes of moderate- and high-intensity interval training on serum Salusin-α and Salusin-β and lipid profile in women with overweight/obesity.

Subjects and Methods

A number of forty females were assigned to each of (1) Control (BMI= 30.2 ± 2.8 kg/m2, n=14), (2) Moderate-intensity (BMI= 31.2 ±3.3 kg/m2, n=13) and (3) High-intensity interval training (BMI=30.9±3.4 kg/m2, n=13) groups. The subjects of experimental groups participated in the selected interval trainings for eight weeks. The first blood sampling was performed within 48 hours prior to the first training session and the second samples were obtained 48 hours after the last training session.

Results

The findings revealed that there were significant increases in Salusin-α (36% vs. 3%; p = 0.001) and high-density lipoprotein levels (7% vs. 5%; P = 0.039), while significant reductions in the levels of Triglyceride (−8% vs. −9%; p= 0.012) and total cholesterol (−1% vs. −8%; P =0.01) levels of moderate- and high-intensity interval training groups, respectively. Also, there were insignificant changes in Salusin-β (−7% vs. −5%; P = 0.108), low-density lipoproteins (−3% vs. −11%; P =0.046) and very-low-density lipoprotein (−10% vs. −8%; P = 0.056) compared to control group. There were only significant differences between Salusin-α and high-density lipoprotein levels of training groups (P<0.05).

Conclusion

It is suggested that, although improvements in lipid profile was nearly similar for two training modes, moderate intensity interval training was more effective to prevent and control atherosclerosis.

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<![CDATA[A Vaccine Against Group B Streptococcus: Recent Advances]]> https://www.researchpad.co/product?articleinfo=N88ff99ec-00ee-497f-bcc2-4853da710b46

Abstract

Group B streptococcus (GBS) causes a high burden of neonatal and infant disease globally. Implementing a vaccine for pregnant women is a promising strategy to prevent neonatal and infant GBS disease and has been identified as a priority by the World Health Organisation (WHO). GBS serotype-specific polysaccharide – protein conjugate vaccines are at advanced stages of development, but a large number of participants would be required to undertake Phase III clinical efficacy trials. Efforts are therefore currently focused on establishing serocorrelates of protection in natural immunity studies as an alternative pathway for licensure of a GBS vaccine, followed by Phase IV studies to evaluate safety and effectiveness. Protein vaccines are in earlier stages of development but are highly promising as they might confer protection irrespective of serotype. Further epidemiological, immunological and health economic studies are required to enable the vaccine to reach its target population as soon as possible.

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<![CDATA[Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment]]> https://www.researchpad.co/product?articleinfo=N62b92a85-3682-40d4-9a53-128570209595

Purpose

To determine whether cornea nerve fiber density and/or corneal function are valid markers for early detection and treatment of peripheral neuropathy in rats modeling prediabetes and type 2 diabetes.

Methods

High-fat feeding combined without or with low-dose streptozotocin was used to create rat models for prediabetes and type 2 diabetes that were longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. There were three time points examined in each of the three conditions with 12 rats per group. The latest time point (24 weeks of high-fat diet with or without 16 weeks of hyperglycemia) was used to examine reversibility of neuro and vascular pathology following 16 weeks of treatment with menhaden oil, a natural source of long-chain omega-3 polyunsaturated fatty acids. The number of rats in the intervention study ranged from 6 to 17.

Results

Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the pre-diabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil significantly reversed both vascular and peripheral nerve damage induced by chronic obesity or type 2 diabetes.

Conclusion

These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and type 2 diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil are an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.

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<![CDATA[Management of L-Dopa Overdose in the Competitive Inhibition State [Expression of Concern]]]> https://www.researchpad.co/product?articleinfo=N3ccfecd6-2be6-4f71-a47a-120a83aa9129 ]]> <![CDATA[ATF3 Demethylation Promotes the Transcription of ARL4C, Which Acts as a Tumor Suppressor in Human Breast Cancer]]> https://www.researchpad.co/product?articleinfo=Ncb66c365-b2c3-4781-a0c7-b342816abb03

Introduction

Breast cancer is a common malignancy in females worldwide. In this study, we investigated the role of activating transcription factor 3 (ATF3) and ADP-ribosylation factor like-4 (ARL4) in human breast cancer, and the associated mechanisms.

Materials and Methods

We measured ATF3 and ATL4C expressions in 15 paired breast cancer tissues using qRT-PCR, Western blotting and IHC. Cell growth, migration and invasion were tested in ATF3 or ARL4C overexpression breast cancer cells. TCGA database analysis was done to identify the correlation between ATF3 and ARL4C. We evaluated the binding of ATF3 to ARL4C promoter sequences and the effect of hypermethylation and demethylation of ATF3. A meta-analysis was done to investigate the relationship between the expression of ATF3 and/or ARL4C and the poor prognoses.

Results

Our results showed that ATF3 and ARL4C were decreased in breast cancer specimens at both mRNA and protein levels. Restoration of ATF3 or ARL4C reduced breast cancer tumorigenesis, evidenced by decreased cell growth, migration and invasion. The expression of ATF3 was positively correlated with ARL4C in breast cancer specimens, and ATF3 was shown to bind to the ARL4C promoter sequences. Furthermore, the expression of ATF3 was negatively regulated by hypermethylation, and demethylation of ATF3 stimulated ATF3 expression, which further promoted ARL4C transcription. Finally, a meta-analysis showed that patients with breast cancer with lower expression levels of ATF3 and/or ARL4C had worse prognoses.

Conclusion

Our results suggest that the ATF3/ARL4C axis may be a prospective biomarker for diagnosis and determination of prognosis, and a potential target for breast cancer treatment.

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<![CDATA[Detrimental Effect of C-Reactive Protein on the Cardiometabolic Cells and Its Rectifying by Metabolic Surgery in Obese Diabetic Patients]]> https://www.researchpad.co/product?articleinfo=N0efea14f-073f-4215-9b65-daade5f56cdb

Background

High-sensitivity C-reactive protein (hs-CRP) has been regarded as a biomarker of low-degree inflammation in illness; however, whether CRP exerts its pathogenic effect on the cardiometabolic system remains unknown. Aside from the beneficial effects of metabolic surgery on cardiometabolic system, its impact on inflammation still worth examining. Thus, this study aims to investigate the effect of CRP on adipose and vascular cells, and their responses to metabolic surgery in obese diabetic patients.

Patients and Methods

The expression of CRP and RAS- and ERK-related factors in the adipocytes and VSMCs were measured. Obese patients with type 2 diabetes who underwent metabolic surgery were followed up for 2 years thereafter. Laboratory tests, which included serum hs-CRP levels and visceral fat thickness (VFT), were obtained before and after surgery.

Results

CRP administration significantly and dose-dependently increased the intracellular-free calcium concentration ([Ca2+]i) in cultured adipocytes and in the VSMCs. CRP administration significantly increased ACE, Ang II, AT1R and p-ERK expressions, but reduced ACE2 expression in both the adipocytes and VSMCs. Clinical study showed that VFT was closely associated with serum hs-CRP. Furthermore, VFT and serum hs-CRP were found to be highly associated with blood pressure. Finally, metabolic surgery remarkably decreased blood pressure, visceral fat and serum hs-CRP levels.

Conclusion

CRP has a detrimental effect on cardiometabolic cells, aside from functioning merely as a biomarker. Serum hs-CRP levels are highly associated with hypertension and visceral obesity, which can be antagonized by metabolic surgery in obese diabetic patients.

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