The use of fecal microbiota transplant in sepsis
Sepsis is defined as a dysregulated inflammatory response, which ultimately results from a perturbed interaction of both an altered immune system and the biomass and virulence of involved pathogens.   This response has been tied to the intestinal microbiota, as the microbiota and its associated metabolites play an essential role in regulating the host immune response to infection.  In turn, critical illness as well as necessary healthcare treatments result in a collapse of the intestinal mic robiota diversity and a subsequent loss of health-promoting short chain fatty acids, such as butyrate, leading to the ...
Source: Translational Research - July 7, 2020 Category: Research Authors: Robert Keskey, Jennifer T Cone, Jennifer R DeFazio, John C Alverdy Source Type: research

Mechanisms and biomarkers of cancer-associated thrombosis
Cancer-associated thrombosis is a leading cause of non-cancer death in cancer patients and is comprised of both arterial and venous thromboembolism. There are multiple risk factors for developing VTE, including cancer type, stage, treatment, and other medical comorbidities, which suggests that the etiology of thrombosis is multifactorial. While cancer-associated thrombosis can be treated with anticoagulation, benefits of therapy must be balanced with the increased bleeding risks seen in patients with cancer. (Source: Translational Research)
Source: Translational Research - July 6, 2020 Category: Research Authors: Ann S. Kim, Alok A. Khorana, Keith R. McCrae Source Type: research

Induction of autophagy by Beclin-1 in granulosa cells contributes to follicular progesterone elevation in ovarian endometriosis
This study aimed to investigate the autophagic activity in ovarian granulosa cells (GCs) of patients with endometriosis and to clarify the role of BECN1 in preovulatory P4 elevation. (Source: Translational Research)
Source: Translational Research - July 5, 2020 Category: Research Authors: Ying Ding, Qinling Zhu, Yaqiong He, Yao Lu, Yuan Wang, Jia Qi, Hasiximuke Wu, Rui Xu, Jiaxing Li, Xinyu Li, Yun Sun Source Type: research

IL-10-producing NK cells exacerbate sublethal Streptococcus pneumoniae infection in the lung
Lung inflammation is tightly controlled to balance microbial clearance with the tissue damage that accompanies this response. Bacterial pathogens including Streptococcus pneumoniae modulate immune regulation by promoting secretion of the anti-inflammatory cytokine IL-10. The important cellular sources of IL-10 that impact protection against different bacterial infections are not well characterized. We find that S. pneumoniae activates IL-10 secretion from natural killer (NK) cells in the lung, which restrict host protection in a mouse model of sublethal infection. (Source: Translational Research)
Source: Translational Research - July 4, 2020 Category: Research Authors: Sarah E. Clark, Rebecca L. Schmidt, Elizabeth R. Aguilera, Laurel L. Lenz Source Type: research

IcyHot analgesic topical cream limits cardiac injury in rodents
Little is known whether topical analgesic creams, whose natural products enter the blood stream after application, affect myocardial infarct size. Here we tested whether topical analgesic creams can trigger remote cardioprotection and the mechanism involved.Male Sprague Dawley rats were used for an in vivo rodent model consisting of 30 minutes left anterior descending coronary artery ischemia and 2 hours of reperfusion followed by infarct size assessment. The topical analgesic IcyHot, applied to the abdomen prior to ischemia, reduced myocardial infarct size versus control (41 ±3* versus 62±1, n=6/group, *P (S...
Source: Translational Research - July 3, 2020 Category: Research Authors: Yun Wu, Annabel W. Chen, Candida L. Goodnough, Yao Lu, Ye Zhang, Eric R. Gross Tags: Original Article Source Type: research

The Acute Respiratory Distress Syndrome Biomarker Pipeline: Crippling Gaps between Discovery and Clinical Utility
Recent innovations in translational research have ushered an exponential increase in the discovery of novel biomarkers, thereby elevating the hope for deeper insights into “personalized” medicine approaches to disease phenotyping and care. However, a critical gap exists between the fast pace of biomarker discovery and the successful translation to clinical use. This gap underscores the fundamental biomarker conundrum across various acute and chronic disorders: how does a biomarker address a specific unmet need? Additionally, the gap highlights the need to shift the paradigm from a focus on biomarker discovery t...
Source: Translational Research - June 26, 2020 Category: Research Authors: Christian Bime, Sara M. Camp, Nancy Casanova, Radu C. Oita, Juliet Ndukum, Heather Lynn, Joe G.N. Garcia Tags: Review Article Source Type: research

Hormones and Thrombosis: Risk Across the Reproductive Years and Beyond
Endogenous and exogenous hormones have significant effects  on coagulation and may tip the hemostatic balance toward thrombosis. The endogenous hormonal changes in pregnancy and polycystic ovary syndrome, and exogenous hormonal contraception, menopause replacement, and transgender cross-hormone replacement may increase thromboembolism risk. Using t he lowest effective dose is critical for prevention, but once thrombosis occurs, anticoagulation may be required, in some, long-term. We review the relative risk of thrombosis in these conditions, risk fa...
Source: Translational Research - June 26, 2020 Category: Research Authors: Nicoletta Machin, Margaret V. Ragni Tags: Review Article Source Type: research

Autologous fecal microbiota transplantation for the treatment of inflammatory bowel disease
The term autologous fecal microbiota transplantation (a-FMT) refers herein to the use of one's feces during a healthy state for later use to restore gut microbial communities after perturbations. Generally, heterologous fecal microbiota transplantation (h-FMT), where feces from a ``healthy ” donor is transplanted into a person with illness, has been used to treat infectious diseases such as recurrent Clostridioides difficile infection (CDI), with cure rates of up to 90%. In humans, due to limited response to medicines, h-FMT has become a hallmark intervention to treat CDI. (Source: Translational Research)
Source: Translational Research - June 22, 2020 Category: Research Authors: Abigail R Basson, Yibing Zhou, Brian Seo, Alexander Rodriguez-Palacios, Fabio Cominelli Tags: Review Article Source Type: research

Contents
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Masthead
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Editorial Advisory Board
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Author Guidelines
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Information for Readers
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Contents
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Source: Translational Research - June 20, 2020 Category: Research Source Type: research

Cellular senescence in age-related disorders
Much of the population is now faced with an enormous burden of age-associated chronic diseases. Recent discoveries in geroscience indicate that healthspan in model organisms such as mice can be manipulated by targeting cellular senescence, a hallmark mechanism of aging, defined as an irreversible proliferative arrest that occurs when cells experience oncogenic or other diverse forms of damage. Senescent cells and their pro-inflammatory secretome have emerged as contributors to age-related tissue dysfunction and morbidity. (Source: Translational Research)
Source: Translational Research - June 19, 2020 Category: Research Authors: Japneet Kaur, Joshua N. Farr Source Type: research

The selective PPAR-delta agonist seladelpar reduces ethanol-induced liver disease by restoring gut barrier function and bile acid homeostasis in mice
Alcohol-associated liver disease is accompanied by dysregulation of bile acid metabolism and gut barrier dysfunction. Peroxisome proliferator-activated receptor-delta (PPAR δ) agonists are key metabolic regulators and have anti-inflammatory properties. Here, we evaluated the effect of the selective PPAR-delta agonist seladelpar (MBX‐8025) on gut barrier function and bile acid metabolism in a mouse model of ethanol-induced liver disease. Wild type C57BL/6 mice were f ed Lieber DeCarli diet containing 0% to 36% ethanol (caloric) for 8 weeks followed by a single binge of ethanol (5g/kg). (Source: Translational Research)
Source: Translational Research - June 15, 2020 Category: Research Authors: Huikuan Chu, Lu Jiang, Bei Gao, Nagsen Gautam, Jawaher A. Alamoudi, Sonja Lang, Yanhan Wang, Yi Duan, Yazen Alnouti, Edward E. Cable, Bernd Schnabl Source Type: research

Current opinion and emerging trends on the treatment, diagnosis, and prevention of pregnancy-associated venous thromboembolic disease: a review
Pregnancy associated venous thromboembolism (PA-VTE) is a leading cause of maternal morbidity and mortality worldwide. Despite the availability of international guidance on the prevention, diagnosis and treatment, practice differs between countries and clinical institutions. The evidence base in this area is limited due to the vulnerable population who are affected, with the majority of guidelines deriving their recommendations from experience in surgical and medical venous thromboembolic disease. (Source: Translational Research)
Source: Translational Research - June 14, 2020 Category: Research Authors: Fergal O'Shaughnessy, Daniel O'Reilly, Fionnuala N í Áinle Tags: Review article Source Type: research

Current opinion and emerging trends on the treatment, diagnosis and prevention of pregnancy-associated venous thromboembolic disease: a review
Pregnancy Associated Venous Thromboembolism (PA-VTE) is a leading cause of maternal morbidity and mortality worldwide. Despite the availability of international guidance on the prevention, diagnosis and treatment, practice differs between countries and clinical institutions. The evidence base in this area is limited due to the vulnerable population who are affected, with the majority of guidelines deriving their recommendations from experience in surgical and medical venous thromboembolic disease. (Source: Translational Research)
Source: Translational Research - June 14, 2020 Category: Research Authors: Fergal O'Shaughnessy, Daniel O'Reilly, Fionnuala N í Áinle Source Type: research

Downregulating the P2X3 receptor in the carotid body to reduce blood pressure via acoustic gene delivery in canines
The purinergic P2X3 receptor in the carotid body (CB) is considered a new target for treating hypertension, although approaches for targeted regulating P2X3 receptor expression are lacking. Here, we explored the feasibility of targeted P2X3 receptor down-regulation in CBs by localized low-intensity focused ultrasound (LIFU)-mediated gene delivery to reduce the blood pressure. Thirty-two Kunming canines were randomly assigned to the treatment group (n  = 14), negative control group (n = 10), LIFU + cationic microbubbles group (n = 4), and LIFU-only group (n = 4). (Source: Translational Research)
Source: Translational Research - June 13, 2020 Category: Research Authors: Qian Xue, Ruiyu Wang, Liang Wang, Bo Xiong, Lingjiao Li, Jun Qian, Lan Hao, Zhigang Wang, Dichuan Liu, Changming Deng, Shunkang Rong, Yuanqing Yao, Yonghong Jiang, Que Zhu, Jing Huang Source Type: research

Downregulating the P2  × 3 Receptor in the Carotid Body to Reduce Blood Pressure via Acoustic Gene Delivery in Canines
The purinergic P2  × 3 receptor in the carotid body (CB) is considered a new target for treating hypertension, although approaches for targeted regulating P2 × 3 receptor expression are lacking. Here, we explored the feasibility of targeted P2 × 3 receptor down-regulation in CBs by localized low-intens ity focused ultrasound (LIFU)-mediated gene delivery to reduce the blood pressure. Thirty-two Kunming canines were randomly assigned to the treatment group (n = 14), negative control group (n = 10), LIFU + cationic microbubbles group (n = 4), and LIFU-only group (n = 4). (Sou...
Source: Translational Research - June 13, 2020 Category: Research Authors: Qian Xue, Ruiyu Wang, Liang Wang, Bo Xiong, Lingjiao Li, Jun Qian, Lan Hao, Zhigang Wang, Dichuan Liu, Changming Deng, Shunkang Rong, Yuanqing Yao, Yonghong Jiang, Que Zhu, Jing Huang Source Type: research

Antisense Antibacterial Compounds
Extensive antibiotic use combined with poor historical drug stewardship practices have created a medical crisis in which once treatable bacterial infections are now increasingly unmanageable. To combat this, new antibiotics will need to be developed and safeguarded. An emerging class of antibiotics based upon nuclease-stable antisense technologies has proven valuable in preclinical testing against a variety of bacterial pathogens. This review describes the current state of development of antisense-based antibiotics, the mechanisms thus far employed by these compounds, and possible future avenues of research. (Source: Translational Research)
Source: Translational Research - June 5, 2020 Category: Research Authors: Reed Pifer, David E. Greenberg Tags: Review Article Source Type: research

Pan-Cancer Analysis of the Developmental Pathways Reveals Non-Canonical Wnt Signaling as a Driver of Mesenchymal-Type Tumors
The processes of angiogenesis, cell proliferation, invasion, and migration, and the signaling pathways that drive these events, are activated in both cancer and during embryonic development. Here, we systematically assessed how the activity of major developmental signaling pathways, represented by the expression of genes encoding components of the pathways, correlated with patient survival in ∼8000 patients across 17 cancer types. We also compared the expressed genes enriched in developmental pathways with those associated with epithelial-mesenchymal transition (EMT) both in a cancer cohort and in mice during embryonic...
Source: Translational Research - June 5, 2020 Category: Research Authors: Andrew Xue, Marina Chan, Taranjit S. Gujral Source Type: research

Kv1.3 blockade Inhibits Proliferation of Vascular Smooth Muscle Cells In Vitro and Intimal Hyperplasia In Vivo
The modulation of voltage-gated K+ (Kv) channels, involved in cell proliferation, arises as a potential therapeutic approach for the prevention of intimal hyperplasia present in in-stent restenosis (ISR) and allograft vasculopathy (AV). We studied the effect of PAP-1, a selective blocker of Kv1.3 channels, on development of intimal hyperplasia in vitro and in vivo in two porcine models of vascular injury. In vitro phenotypic modulation of VSMCs was associated to an increased functional expression of Kv1.3 channels, and only selective Kv1.3 channel blockers were able to inhibit porcine VSMC proliferation. (Source: Translational Research)
Source: Translational Research - June 5, 2020 Category: Research Authors: Joaquim Bobi, Manel Garabito, N úria Solanes, Pilar Cidad, Víctor Ramos-Pérez, Alberto Ponce, Montserrat Rigol, Xavier Freixa, Claudia Pérez-Martínez, Armando Pérez de Prado, Felipe Fernández-Vázquez, Manel Sabaté, Salvador Borrós, José Ramón Source Type: research

Transcription factor HIF1 α promotes proliferation, migration, and invasion of cholangiocarcinoma via long noncoding RNA H19/microRNA-612/Bcl-2 axis
In this study, we investigate the scantly documented interaction of HIF1α and miR-612 in cholangiocarcinoma. We first undertook microarray-based cholangiocarcinoma gene expression profiles to screen out the differentially expressed long noncoding RNAs (lncRNAs) and genes. (Source: Translational Research)
Source: Translational Research - June 4, 2020 Category: Research Authors: Aijun Yu, Luwen Zhao, Qingmin Kang, Jian Li, Kai Chen, Hua Fu Source Type: research

Transcription factor HIF1 α promotes proliferation, migration and invasion of cholangiocarcinoma via long non-coding RNA H19/microRNA-612/Bcl-2 axis
In this study we investigate the scantly documented interaction of HIF1α and miR-612 in cholangiocarcinoma. We first undertook microarray-based cholangiocarcinoma gene expression profiles to screen out the differentially expressed long non-coding RNAs (lncRNAs) and genes. (Source: Translational Research)
Source: Translational Research - June 4, 2020 Category: Research Authors: Aijun Yu, Luwen Zhao, Qingmin Kang, Jian Li, Kai Chen, Hua Fu Source Type: research

Impact of Saharan dust exposure on airway inflammation in patients with ischemic heart disease
Epidemiological studies found that increases in the concentrations of airborne particulate matter (PM) smaller than 10 microns diameter (PM10) in the ambient air due to desert dust outbreaks contribute to global burden of diseases, primarily as a result of increased risk of cardiovascular morbidity and mortality. No studies have investigated the possible association between desert dust inhalation and airway inflammation in patients with ischemic heart disease (IHD). Induced sputum was collected in 38 patients and analysed to determine markers of airway inflammation (Transforming Growth Factor- β1 [TGF-β1] and hyd...
Source: Translational Research - June 3, 2020 Category: Research Authors: Alberto Dominguez-Rodriguez, Sergio Rodr íguez, Nestor Baez-Ferrer, Pedro Abreu-Gonzalez, Juan Abreu-Gonzalez, Pablo Avanzas, Manuel Carnero, Cesar Moris, Jessica López-Darias, Daniel Hernández-Vaquero Source Type: research

Innovative highlights of clinical drug trial design
Clinical trials serve as the gold standard to evaluate the efficacy and safety of tested drugs prior to marketing authorization. Nevertheless, there have been a few challenging issues well noted in traditional clinical trials such as tedious processing duration and escalating high costs among others. To improve the efficiency of clinical studies, a spectrum of expedited clinical trial modes has been designed, and selectively implemented in contemporary drug developing landscape. Herein this article presents an update on the innovated human trial designs that are corroborated through coming up with approval of notable thera...
Source: Translational Research - June 2, 2020 Category: Research Authors: Daohong Chen, Eric Yining Qi Source Type: research

Information for Readers
(Source: Translational Research)
Source: Translational Research - June 1, 2020 Category: Research Source Type: research

Contents
(Source: Translational Research)
Source: Translational Research - June 1, 2020 Category: Research Source Type: research

Nuclear NADPH Oxidase-4 Associated With Disease Progression In Renal Cell Carcinoma
Nuclear NADPH oxidase-4 (Nox4) is a key component of metabolic reprogramming and is often overexpressed in renal cell carcinoma (RCC). However, its prognostic role in RCC remains unclear. Here we examined the significance of nuclear Nox4 on disease progression and development of drug resistance in advanced RCC.We analyzed human RCC tissue from multiple regions in the primary index tumor, cancer-associated normal adjacent parenchyma, intravascular tumor in locally advanced cancer patients. We found that the higher nuclear Nox4 expression was significantly associated with progression and death. (Source: Translational Research)
Source: Translational Research - May 31, 2020 Category: Research Authors: Dharam Kaushik, Keith A. Ashcraft, Hanzhang Wang, Karthigayan Shanmugasundaram, Pankil Shah, Gabriela Gonzalez, Alia Nazarullah, Cooper B. Tye, Michael A. Liss, Deepak Pruthi, Ahmed M. Mansour, Wasim Chowdhury, Dean Bacich, Hao Zhang, Amanda L. Watson, Ka Source Type: research

Microvascular thrombosis: experimental and clinical implications
A significant amount of clinical and research interest in thrombosis is focused on large vessels (e.g., stroke, myocardial infarction, deep venous thrombosis, etc.); however, thrombosis is often present in the microcirculation in a variety of significant human diseases, such as disseminated intravascular coagulation, thrombotic microangiopathy, sickle cell disease, and others. Further, microvascular thrombosis has recently been demonstrated in patients with COVID-19, and has been proposed to mediate the pathogenesis of organ injury in this disease. (Source: Translational Research)
Source: Translational Research - May 23, 2020 Category: Research Authors: Monica A. Bray, Sarah A. Sartain, Jahnavi Gollamudi, Rolando E. Rumbaut Tags: Review Article Source Type: research

Insights from experimental post-thrombotic syndrome and potential for novel therapies
Post thrombotic syndrome (PTS) is an end stage manifestation of deep vein thrombosis. This is an inherently inflammatory process, with consequent fibrosis. Multiple cellular types are involved, and are likely driven by leukocytes. Herein, we review the current gaps in therapy, and insights from rodent models of venous thrombosis that suggest possible targets to treat and prevent PTS. (Source: Translational Research)
Source: Translational Research - May 19, 2020 Category: Research Authors: Peter Henke, Sriganesh Sharma, Thomas Wakefield, Dan Myers, Andrea Obi Tags: Review Article Source Type: research

Emerging role of NIK/IKK2-binding protein (NIBP)/Trafficking protein particle complex 9 (TRAPPC9) in nervous system diseases
NF κB signaling and protein trafficking network play important roles in various biological and pathological processes. NIK-and-IKK2-binding protein (NIBP), also known as trafficking protein particle complex 9 (TRAPPC9), is a prototype member of a novel protein family, and has been shown to regulate bo th NFκB signaling pathway and protein transport/trafficking. NIBP is extensively expressed in the nervous system and plays an important role in regulating neurogenesis and neuronal differentiation. NIBP/TRAPPC9 mutations have been linked to an autosomal recessive intellectual disability (ARID) synd rome, called NI...
Source: Translational Research - May 17, 2020 Category: Research Authors: Brittany Bodnar, Arianna DeGruttola, Yuanjun Zhu, Yuan Lin, Yonggang Zhang, Xianming Mo, Wenhui Hu Tags: Review Article Source Type: research

Development and Use of Clinical Practice Guidelines on Venous Thromboembolism
Venous thromboembolism (VTE) is a common disorder associated with substantial morbidity and mortality. It may be encountered by clinicians in virtually all medical specialties and healthcare settings. A large number of clinical practice guidelines (CPGs) on VTE have been published in recent years to support clinicians in delivering high quality care for the prevention, diagnosis, and management of VTE. Essential elements of CPGs include a guideline panel composed of content experts from multiple disciplines, methodologists, and representatives from key affected groups; a systematic review of evidence; consideration of pati...
Source: Translational Research - May 17, 2020 Category: Research Authors: Adam Cuker Source Type: research

Fibrinolytics for the Treatment of Pulmonary Embolism
The use of fibrinolytic agents in acute PE, first described over 50 years ago, hastens the resolution of RV stain, leading to earlier hemodynamic improvement. However, this benefit comes at the increased risk of bleeding. The strongest indication for fibrinolysis is in high-risk PE, or that characterized by sustained hypotension, while its use in patients with intermediate-risk PE remains controversial. Fibrinolysis is generally not recommended for routine use in intermediate-risk PE, although most guidelines advise that it may be considered in patients with signs of acute decompensation and an overall low bleeding risk. (...
Source: Translational Research - May 17, 2020 Category: Research Authors: Lauren K. Stewart, Jeffrey A. Kline Source Type: research

Deubiquitinase USP13 promotes extracellular matrix expression by stabilizing Smad4 in lung fibroblast cells
Smad4 plays a central role in the regulation of extracellular matrix (ECM) protein expression and cell differentiation; however, the molecular regulation of Smad4 protein stability by a deubiquitinase has not been reported. In the current study, we reveal that a deubiquitinase USP13 stabilizes Smad4, ultimately modulating ECM protein expression in lung fibroblast cells. USP13 was increased in primary adult lung fibroblasts isolated from bleomycin-challenged mice and transforming growth factor (TGF)- β1-treated primary mouse lung fibroblasts. (Source: Translational Research)
Source: Translational Research - May 17, 2020 Category: Research Authors: Xinxin Liao, Yanhui Li, Jia Liu, Yingze Zhang, Jiangning Tan, Daniel J. Kass, Mauricio Rojas, Rama Mallapalli, Jing Zhao, Yutong Zhao Source Type: research

PECAM-1 Protects against DIC by Dampening Inflammatory Responses via Inhibiting Macrophage Pyroptosis and Restoring Vascular Barrier Integrity
Disseminated intravascular coagulation (DIC) is a frequent complication of sepsis that affects patient outcomes due to accompanying thrombo-inflammation and microvascular permeability changes. Platelet endothelial cell adhesion molecule-1 (PECAM-1), a cellular adhesion and signaling receptor that is expressed on both hematopoietic and endothelial cells, plays an important anti-inflammatory role in acute and chronic inflammatory disease models. Little is known, however, about role and mechanism of PECAM-1 in septic DIC. (Source: Translational Research)
Source: Translational Research - May 14, 2020 Category: Research Authors: Lili Luo, Min Xu, Danying Liao, Jun Deng, Heng Mei, Yu Hu Source Type: research

Pathogenesis of Heparin-Induced Thrombocytopenia
There are currently no effective substitutes for high intensity therapy with unfractionated heparin (UFH) for cardiovascular procedures based on its rapid onset of action, ease of monitoring and reversibility. The continued use of UFH in these and other settings requires vigilance for its most serious non-hemorrhagic complication, heparin induced thrombocytopenia (HIT). HIT is an immune prothrombotic disorder caused by antibodies that recognize complexes between platelet factor 4 (PF4) and polyanions such as heparin (H). (Source: Translational Research)
Source: Translational Research - May 13, 2020 Category: Research Authors: Gowthami M. Arepally, Douglas B. Cines Source Type: research

Liquid biopsy for breast cancer using extracellular vesicles and cell-free microRNAs as biomarkers
Improvement of breast cancer (BC) patient's outcome is directly related to early detection. However, there is still a lack of reliable biomarkers for diagnosis, prognosis and, treatment follow up in BC, leading researchers to study the potential of liquid biopsy based on circulating microRNAs (c-miRNAs). These c-miRNAs can be cell-free or associated with extracellular vesicles (EVs), and have great advantages such as stability in biofluids, non-invasive accessibility compared to current techniques (core-biopsy and surgery), and expression associated with pathogenic conditions. (Source: Translational Research)
Source: Translational Research - May 12, 2020 Category: Research Authors: Patricia Midori Murobushi Ozawa, Tayana Schultz Jucoski, Evelyn Vieira, Tamyres Mingorance Carvalho, Danielle Malheiros, Enilze Maria de Souza Fonseca Ribeiro Tags: Review Source Type: research

Effects of Estrogen Receptor Signaling on Prostate Cancer Carcinogenesis
Management of advanced prostate cancer remains complex, with substantial changes in treatment options emerging in recent years having implications for treatment selection and sequencing. Recognition of the importance of androgen signaling has led to life-prolonging treatments, as well as “liquid biopsy” techniques to guide these treatments in some settings. Therapies that target estrogen receptor signaling are efficacious but infrequently used options for treatment of castration-resistant prostate cancer (CRPC). (Source: Translational Research)
Source: Translational Research - May 12, 2020 Category: Research Authors: Liang G. Qu, Hady Wardan, Ian D. Davis, Carmel Pezaro, Pavel Sluka Tags: Review Article Source Type: research

Antiphospholipid Syndrome
Antiphospholipid syndrome (APS) is one of the more common acquired causes of hypercoagulability. Its major presentations are thrombotic (arterial, venous or microvascular) and pregnancy morbidity (miscarriages, late intrauterine fetal demise, and severe pre-eclampsia). Classification criteria include three different antiphospholipid antibodies: lupus anticoagulant; anticardiolipin; and anti-beta 2 glycoprotein I. Management includes both preventive strategies (low dose aspirin, hydroxychloroquine) and long-term anticoagulation after thrombosis. (Source: Translational Research)
Source: Translational Research - May 12, 2020 Category: Research Authors: Michelle Petri Tags: Review Article Source Type: research

Venous thrombosis of the liver: current and emerging concepts in management
Venous thrombosis within the hepatic vasculature is associated with a distinct array of risk factors, characteristics, and potential complication. As such, it entails unique management considerations and strategies relative to the more common categories of venous thromboembolic disease. Although broadly divided into thrombosis of the afferent vasculature (the portal venous system) and efferent vasculature (the hepatic venous system), presentations and management strategies within these groupings are heterogeneous. (Source: Translational Research)
Source: Translational Research - May 11, 2020 Category: Research Authors: Leonard Naymagon Tags: Review Article Source Type: research

Therapeutic Vaccines for the Treatment of HIV
Despite the success of anti-retroviral therapy (ART) in transforming HIV into manageable disease, it has become evident that long-term ART will not eliminate the HIV reservoir and cure the infection. Alternative strategies to eradicate HIV infection, or at least induce a state of viral control and drug-free remission are therefore needed. Therapeutic vaccination aims to induce or enhance immunity to alter the course of a disease. In this review we provide an overview of the current state of therapeutic HIV vaccine research and summarize the obstacles that the field faces while highlighting potential ways forward for a stra...
Source: Translational Research - May 10, 2020 Category: Research Authors: Zhilin Chen, Boris Julg Tags: Review Article Source Type: research

New and alternative strategies for the prevention, control, and treatment of antibiotic-resistant Campylobacter
Campylobacter is an enteric pathogen and a leading bacterial cause of diarrhea worldwide. It is widely distributed in food animal species and is transmitted to humans primarily through the foodborne route. While generally causing self-limited diarrhea in humans, Campylobacter may induce severe or systemic infections in immunocompromised or young/elderly patients, which often requires antibiotic therapy with the first-line antibiotics including fluoroquinolones and macrolides. Over the past decades, Campylobacter has acquired resistance to these clinically significant antibiotics, compromising the effectiveness of antibioti...
Source: Translational Research - May 10, 2020 Category: Research Authors: Lei Dai, Orhan Sahin, Madhusudan Grover, Qijing Zhang Tags: Review Article Source Type: research

Baseline urinary metabolites predict albuminuria response to spironolactone in type 2 diabetes
The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in subjects with diabetic kidney disease (DKD), albeit with a large variability between individuals. Identifying novel biomarkers that predict response to therapy may help to tailor spironolactone therapy. We aimed to identify a set of metabolites for prediction of albuminuria response to spironolactone in subjects with type 2 diabetes. Systems biology molecular process analysis was performed a priori to identify metabolites linked to molecular disease processes and drug mechanism of action. (Source: Translational Research)
Source: Translational Research - May 10, 2020 Category: Research Authors: Skander Mulder, Paul Perco, Christina Oxlund, Uzma F. Mehdi, Thomas Hankemeier, Ib A. Jacobsen, Robert Toto, Hiddo J.L. Heerspink, Michelle J. Pena Source Type: research

Cathepsin B deficiency ameliorates liver lipid deposition, inflammatory cell infiltration, and fibrosis after diet-induced nonalcoholic steatohepatitis
This study tested the roles of cysteine protease cathepsin B (CatB) in mouse NASH development. Immunoblot revealed increased liver CatB expression in NASH mice. Fructose-palmitate-cholesterol diet increased body weight gain, liver to body weight ratio, blood fasting glucose, plasma total cholesterol and alanine transaminase levels, and liver triglyceride, but decreased plasma high-density lipoprotein in wild-type mice. (Source: Translational Research)
Source: Translational Research - May 10, 2020 Category: Research Authors: Wenqian Fang, Zhiyong Deng, Feriel Benadjaoud, Chongzhe Yang, Guo-Ping Shi Source Type: research

Atrial arrhythmogenesis in a rabbit model of chronic obstructive pulmonary disease
This study investigated the effects of COPD on AF triggers (pulmonary veins, PVs) and substrates (atria), and their potential underlying mechanisms. Electrocardiographic, echocardiographic, and biochemical studies were conducted in control rabbits and rabbits with human leukocyte elastase (0.3 unit/kg)-induced COPD. Conventional microelectrode, Western blotting, and histological examinations were performed on PV, left atrium (LA), right atrium, and sinoatrial node (SAN) preparations from control rabbits and those with COPD. (Source: Translational Research)
Source: Translational Research - May 10, 2020 Category: Research Authors: Chao-Shun Chan, You Shuei Lin, Yung-Kuo Lin, Yao-Chang Chen, Yu-Hsun Kao, Chun-Chun Hsu, Shih-Ann Chen, Yi-Jen Chen Source Type: research

Pathobiology of Frailty in Lung Disease
Frailty is a clinical state of vulnerability to stressors resulting from cumulative alterations in multiple physiological and molecular systems. Frailty assessment in patients with chronic disease is useful for identifying those who are at increased risk for poor clinical and patient reported outcomes. Due to biobehavioral changes purported to cause both frailty and certain chronic lung diseases, patients with lung disease appear susceptible to frailty and prone to developing it decades earlier than community dwelling healthy populations. (Source: Translational Research)
Source: Translational Research - May 3, 2020 Category: Research Authors: Brittany Koons, John Greenland, Joshua Diamond, Jonathan Singer Source Type: research

Disrupted Diurnal Oscillation of Gut-Derived Short Chain Fatty Acids in Shift Workers Drinking Alcohol: Possible Mechanism for Loss of Resiliency of Intestinal Barrier in Disrupted Circadian Host
Microbiota derived short chain fatty acids (SCFAs) are produced by fermentation of non-digestible fiber, and are a key component in intestinal barrier homeostasis. Since the microbiome has diurnal fluctuations, we hypothesized that SCFAs in humans have a diurnal rhythm and their rhythmicity would be impacted by the host central circadian misalignment (night shift work) which would make intestinal barrier more susceptible to disruption by alcohol. To test this hypothesis, we studied three groups of subjects: patients with alcohol use disorder, but no liver disease (AD), healthy day workers (DW), and night workers (NW). (Sou...
Source: Translational Research - May 3, 2020 Category: Research Authors: Garth R. Swanson, Joel Siskin, Annika Gorenz, Maliha Shaikh, Shohreh Raeisi, Louis Fogg, Christopher Forsyth, Ali Keshavarzian Source Type: research

The Gut Microbiome and Frailty
The human microbiome is constituted by an extensive network of organisms that lie at the host/environment interface and transduce signals that play vital roles in human health and disease across the lifespan. Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes including death. While recent studies suggest the microbiome may impact key pathways critical to frailty pathophysiology, direct evaluation of the microbiome-frailty relationship remains limited. (Source: Translational Research)
Source: Translational Research - April 30, 2020 Category: Research Authors: Damani A. Piggott, Susan Tuddenham Source Type: research