scholarly journals Molecular Mechanisms and Emerging Therapeutics for Osteoporosis

2020 ◽  
Vol 21 (20) ◽  
pp. 7623 ◽  
Author(s):  
Ji-Yoon Noh ◽  
Young Yang ◽  
Haiyoung Jung
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Options ◽  
Risk Groups ◽  
The United States ◽  
Bone Architecture ◽  
Global Challenge ◽  
Emerging Therapies ◽  
Metabolic Bone ◽  
Increased Risk ◽  
Control Disease

Osteoporosis is the most common chronic metabolic bone disease. It has been estimated that more than 10 million people in the United States and 200 million men and women worldwide have osteoporosis. Given that the aging population is rapidly increasing in many countries, osteoporosis could become a global challenge with an impact on the quality of life of the affected individuals. Osteoporosis can be defined as a condition characterized by low bone density and increased risk of fractures due to the deterioration of the bone architecture. Thus, the major goal of treatment is to reduce the risk for fractures. There are several treatment options, mostly medications that can control disease progression in risk groups, such as postmenopausal women and elderly men. Recent studies on the basic molecular mechanisms and clinical implications of osteoporosis have identified novel therapeutic targets. Emerging therapies targeting novel disease mechanisms could provide powerful approaches for osteoporosis management in the future. Here, we review the etiology of osteoporosis and the molecular mechanism of bone remodeling, present current pharmacological options, and discuss emerging therapies targeting novel mechanisms, investigational treatments, and new promising therapeutic approaches.

scholarly journals The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists for the Management of NAFLD

2021 ◽  
Author(s):  
Chandani Patel Chavez ◽  
Kenneth Cusi ◽  
Sushma Kadiyala
Keyword(s):  
Evidence Synthesis ◽  
Clinical Care ◽  
Treatment Options ◽  
Critical Role ◽  
Risk Groups ◽  
The United States ◽  
Multidisciplinary Teams ◽  
Consensus Statements ◽  
Meta Analyses

Abstract Context The burden of cirrhosis from NAFLD is reaching epidemic proportions in the United States. This calls for greater awareness among endocrinologists, who often see but may miss the diagnosis in adults with obesity or type 2 diabetes mellitus (T2D) who are at the highest risk. At the same time, recent studies suggest that GLP-1RAs are beneficial versus steatohepatitis (NASH) in this population. This minireview aims to assist endocrinologists to recognize the condition and recent work on the role of GLP-1RAs in NAFLD/NASH. Evidence acquisition Evidence from observational studies, randomized controlled trials, and meta-analyses. Evidence Synthesis Endocrinologists should lead multidisciplinary teams to implement recent consensus statements on NAFLD that call for screening and treatment of clinically significant fibrosis to prevent cirrhosis, especially in the high-risk groups (i.e., people with obesity, prediabetes or T2D). With no FDA-approved agents, weight loss is central to their successful management, with pharmacological treatment options limited today to vitamin E (in people without T2D) and diabetes medications that reverse steatohepatitis, such as pioglitazone or GLP-1RA. Recently the benefit of GLP-1RAs in NAFLD, suggested from earlier trials, has been confirmed in adults with biopsy-proven NASH. In 2021, the FDA also approved semaglutide for obesity management. Conclusion A paradigm change is developing between the endocrinologist’s greater awareness about their critical role to curve the epidemic of NAFLD and new clinical care pathways that include a broader use of GLP-1RAs in the management of these complex patients.

scholarly journals Hepatocellular Carcinoma and Obesity, Type 2 Diabetes Mellitus, Cardiovascular Disease: Causing Factors, Molecular Links, and Treatment Options

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunye Zhang ◽  
Shuai Liu ◽  
Ming Yang
Keyword(s):  
Diabetes Mellitus ◽  
Hepatocellular Carcinoma ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
The United States ◽  
Pathologic Features

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, which will affect more than a million people by the year 2025. However, current treatment options have limited benefits. Nonalcoholic fatty liver disease (NAFLD) is the fastest growing factor that causes HCC in western countries, including the United States. In addition, NAFLD co-morbidities including obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) promote HCC development. Alteration of metabolites and inflammation in the tumor microenvironment plays a pivotal role in HCC progression. However, the underlying molecular mechanisms are still not totally clear. Herein, in this review, we explored the latest molecules that are involved in obesity, T2DM, and CVDs-mediated progression of HCC, as they share some common pathologic features. Meanwhile, several therapeutic options by targeting these key factors and molecules were discussed for HCC treatment. Overall, obesity, T2DM, and CVDs as chronic metabolic disease factors are tightly implicated in the development of HCC and its progression. Molecules and factors involved in these NAFLD comorbidities are potential therapeutic targets for HCC treatment.

scholarly journals Current progress of fluoroquinolones-increased risk of aortic aneurysm and dissection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Cui Jun ◽  
Bian Fang
Keyword(s):  
Aortic Aneurysm ◽  
Molecular Mechanisms ◽  
False Lumen ◽  
The United States ◽  
Black Box ◽  
Research Progress ◽  
Major Life ◽  
Increased Risk ◽  
Aortic Aneurysm And Dissection ◽  
Black Box Warnings

AbstractAortic aneurysm (AA) and aortic dissection (AD) are major life-threatening diseases around the world. AA is a localized or diffuse dilation of the aorta, while AD is the separation of the layers creating a false lumen within the aortic wall. Fluoroquinolones (FQ) remain one of the most important kind of antibiotics and have a wider clinical use and broad antibacterial spectrum. FQ were also reported to treat infected AA. The most common adverse events (AEs) of FQ are mild and reversible, like headaches, diarrhea and nausea. Due to FQ-related serious AEs, such as tendonitis and tendon rupture, chondrotoxicity, or retinal detachment, QT-prolongation and dysglycemia, the United States Food and Drug Administration (FDA) issued a black box warning for FQ for systemic use in 2016 and updated warnings for FQ several times since then. Of note, in December 2018, FDA issued several “black box warnings” against FQ with the latest safety announcement warning about an increased risk of ruptures in the aorta blood vessel in certain patients. Recently, many studies have indicated an association between FQ and an increase risk of AA and AD. However, the exact mechanism of FQ-induced AA/AD remains unclear. This review aims to highlight the latest research progress of the alarming association between FQ and AA/AD. Moreover, molecular mechanisms of FQ in increasing risk of AA and AD are explored. Hopefully, this review can provide novel insights into FQ-increased the risk of AA/AD and a starting place for stewardship interventions.

Pharmacological Treatments for Unipolar Depression

2015 ◽  
Author(s):  
Stefania Prendes-Alvarez ◽  
Alan F. Schatzberg ◽  
Charles B. Nemeroff
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Age Of Onset ◽  
Treatment Options ◽  
Unipolar Depression ◽  
The United States ◽  
Major Depressive ◽  
Medical Disorders ◽  
Increased Risk ◽  
Dsm Iv

Major depressive disorder is a chronic syndrome associated with high mortality (secondary to suicide and increased risk for heart disease, stroke, and other serious diseases). It is one of the most common medical disorders affecting adults in the world today. In the United States, the lifetime prevalence of major depression is 16.7% for adults. The average age of onset is 32 years, and women are 70% more likely to develop depression than men. Neither the core requisite symptoms for the diagnosis of a major depressive episode nor the required duration of at least 2 weeks has changed from DSM-IV to DSM-5. This chapter discusses the main issues surrounding the treatment of major depressive disorder, such as suicidality and goals of treatment, and provides information about all treatment options approved by the U.S. Food & Drug Administration. Drugs are categorized by their mechanisms of action.

scholarly journals Receptor Tyrosine Kinases as Therapeutic Targets in Rhabdomyosarcoma

Sarcoma ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Lisa E. S. Crose ◽  
Corinne M. Linardic
Keyword(s):  
Tyrosine Kinases ◽  
Molecular Mechanisms ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Risk Groups ◽  
Current Treatment ◽  
Childhood And Adolescence ◽  
Surface Receptors ◽  
Genetic Abnormalities ◽  
Blocking Antibodies

Rhabdomyosarcomas (RMSs) are the most common soft tissue sarcomas of childhood and adolescence. To date, there are no effective treatments that target the genetic abnormalities in RMS, and current treatment options for high-risk groups are not adequate. Over the past two decades, research into the molecular mechanisms of RMS has identified key genes and signaling pathways involved in disease pathogenesis. In these studies, members of the receptor tyrosine kinase (RTK) family of cell surface receptors have been characterized as druggable targets for RMS. Through small molecule inhibitors, ligand-neutralizing agents, and monoclonal receptor-blocking antibodies, RTK activity can be manipulated to block oncogenic properties associated with RMS. Herein, we review the members of the RTK family that are implicated in RMS tumorigenesis and discuss both the problems and promise of targeting RTKs in RMS.

Systematic review of economic evidence for the detection, diagnosis, treatment, and follow-up of colorectal cancer in the United Kingdom

2009 ◽  
Vol 25 (4) ◽  
pp. 470-478 ◽  
Author(s):  
Paul Tappenden ◽  
Jim Chilcott ◽  
Alan Brennan ◽  
Hazel Pilgrim
Keyword(s):  
Colorectal Cancer ◽  
Systematic Review ◽  
Treatment Options ◽  
Population Level ◽  
Risk Groups ◽  
Evidence Base ◽  
Economic Evaluations ◽  
Economic Evidence ◽  
Increased Risk

Objectives: The aim of this study was to examine the availability and consistency of economic evidence for the detection, diagnosis, treatment, and follow-up of colorectal cancer.Methods: A systematic review of UK economic evaluations of colorectal cancer interventions was undertaken. Searches were undertaken across ten electronic databases. Studies were critically appraised through reference to a conceptual model of UK colorectal cancer services.Results: Forty-seven studies met the inclusion criteria. There is a substantial economic evidence base surrounding population-level colorectal screening, surgical procedures, and cytotoxic therapies for the adjuvant and palliative treatment of colorectal cancer. There is limited evidence concerning the diagnosis of suspected colorectal cancer, curative treatments for metastatic disease and follow-up regimens for nonmetastatic disease. No studies were identified relating to the economics of radiotherapy, surveillance of increased-risk groups, end-of-life care, or the management of hereditary colorectal cancer. Where evidence is available, studies are subject to important differences concerning treatment options, decision criteria, and incongruent assumptions concerning the disease and its management.Conclusions: Across many aspects of the colorectal cancer service, current practice appears to have emerged without the consideration or support of economic evidence. There is a need to develop a common understanding how colorectal cancer models should be structured and implemented.

Efficacy of a Meal Replacement Diet Plan Compared to a Food-based Diet Plan after a Period of Weight loss: a Randomized Controlled Trial

2018 ◽  
Vol 3 (2) ◽  
Keyword(s):  
Controlled Trial ◽  
Treatment Options ◽  
The United States ◽  
Meal Replacement ◽  
Nonalcoholic Fatty Liver ◽  
Diet Plan ◽  
Psychological Disturbances ◽  
Increased Risk ◽  
Prevalence Of Obesity ◽  
And Oxidative Stress

Obesity is a chronic, complex, multifactorial disorder that has reached epidemic proportions in the United States [1]. Currently, an estimated 66% of the population is categorized as overweight or obese, and 32.2% obese [1,2]. Obesity is associated with an increased risk of morbidity and mortality secondary to complicating conditions that include heart disease, diabetes, cancer, asthma, sleep apnea, arthritis, reproductive complications, and psychological disturbances [3]. Moreover, obesity is associated with greater degrees of inflammation and oxidative stress, which have recently been shown to underlie many chronic conditions, from cardiovascular disease and cancer, to metabolic syndrome and nonalcoholic fatty liver disease, to neurodegenerative diseases, like Parkinson's disease [4,5-7]. Given the prevalence of obesity, its harmful consequences on human health, and the lack of effective treatment options, meal replacement diet plans represent a viable strategy for controlling weight and positively impacting health outcomes.

scholarly journals 995. Effectiveness of Influenza Vaccine for Prevention of Influenza-Associated Hospitalizations Among High-Risk Adults in the United States, 2015–2016

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S296-S296
Author(s):  
Elif Alyanak ◽  
Manjusha Gaglani ◽  
Emily T Martin ◽  
Arnold S Monto ◽  
Don Middleton ◽  
...  
Keyword(s):  
High Risk ◽  
Influenza Vaccine ◽  
Chronic Conditions ◽  
Medical Condition ◽  
Respiratory Illness ◽  
Risk Groups ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Increased Risk ◽  
Research Grant

Abstract Background Individuals with cardiopulmonary and other chronic conditions are at increased risk for severe complications of influenza. Few studies have examined influenza vaccine effectiveness (VE) in high-risk groups. We evaluated VE against influenza-associated hospitalization among adults with specific high-risk conditions. Methods Adults hospitalized with acute respiratory illness (ARI) during the 2015–2016 influenza season were enrolled at eight hospitals participating in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) study. Respiratory specimens were tested for influenza by reverse transcription PCR. Measures of illness severity, underlying health status, and vaccination were obtained from medical records and enrollment interviews. The presence of high-risk conditions was determined from clinical codes assigned to prior year medical encounters. We estimated VE using a test-negative design as (1 − adjusted odds ratio), comparing odds of PCR-confirmed influenza among vaccinated patients vs. unvaccinated controls. Multivariate logistic regression was adjusted for age, sex, and other factors, stratifying by chronic conditions. Results Of 1,467 adults hospitalized with ARI, 236 (16%) had PCR-confirmed influenza; 180 (78%) were A(H1N1)pdm09. In all, 1,358 (93%) had ≥1 high-risk medical condition, and 1,026 (70%) had ≥3 conditions. Cardiovascular (n = 835), metabolic (including diabetes) (n = 773) and lung conditions (n = 692) were most common (figure). Patients with ≥1 high-risk conditions were more likely to be vaccinated (70%) vs. patients not at high risk (31%, P < 0.001). Among all patients, VE against any influenza-associated hospitalization was 50% (95% CI: 31–63). VE was similarly high among patients with neurologic (VE = 64%, 95% CI: 26–83), metabolic (VE = 55%, 95% CI: 30–71), and cardiovascular (VE = 53%, 95% CI: 27–69) conditions, though lower for patients with immunosuppression and malignancy (VE = 20%, 95% CI: −42–54). Conclusion Vaccination significantly reduced risk of influenza hospitalization among adults with the most prevalent high-risk cardiovascular, metabolic, and lung conditions. Results support the benefit of vaccinating adults with existing specific chronic conditions. Disclosures H. K. Talbot, sanofi pasteur: Investigator, Research grant. Gilead: Investigator, Research grant. MedImmune: Investigator, Research grant. Vaxinnate: Safety Board, none. Seqirus: Safety Board, none.

scholarly journals Oxidative ornithine metabolism supports non-inflammatory C. difficile colonization

2022 ◽  
Author(s):  
Kali M. Pruss ◽  
Fatima Enam ◽  
Eric Battaglioli ◽  
Mary DeFeo ◽  
Oscar R. Diaz ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
The United States ◽  
Wild Type ◽  
Targeted Metabolomics ◽  
Disease Symptoms ◽  
Increased Risk ◽  
Infection And Inflammation ◽  
Gnotobiotic Mice ◽  
Single Operon ◽  
Type Strains

AbstractThe enteric pathogen Clostridioides difficile (Cd) is responsible for a toxin-mediated infection that causes more than 200,000 recorded hospitalizations and 13,000 deaths in the United States every year1. However, Cd can colonize the gut in the absence of disease symptoms. Prevalence of asymptomatic colonization by toxigenic Cd in healthy populations is high; asymptomatic carriers are at increased risk of infection compared to noncolonized individuals and may be a reservoir for transmission of Cd infection2,3. Elucidating the molecular mechanisms by which Cd persists in the absence of disease is necessary for understanding pathogenesis and developing refined therapeutic strategies. Here, we show with gut microbiome metatranscriptomic analysis that mice recalcitrant to Cd infection and inflammation exhibit increased community-wide expression of arginine and ornithine metabolic pathways. To query Cd metabolism specifically, we leverage RNA sequencing in gnotobiotic mice infected with two wild-type strains (630 and R20291) and isogenic toxin-deficient mutants of these strains to differentiate inflammation-dependent versus -independent transcriptional states. A single operon encoding oxidative ornithine degradation is consistently upregulated across non-toxigenic Cd strains. Combining untargeted and targeted metabolomics with bacterial and host genetics, we demonstrate that both diet- and host-derived sources of ornithine provide a competitive advantage to Cd, suggesting a mechanism for Cd persistence within a non-inflammatory, healthy gut.

scholarly journals The disease of theories: unravelling the mechanisms of pre-eclampsia

2017 ◽  
Vol 39 (1) ◽  
pp. 22-25 ◽  
Author(s):  
Eric M. George
Keyword(s):  
United States ◽  
Cardiovascular Disease ◽  
Premature Birth ◽  
Molecular Mechanisms ◽  
The United States ◽  
Life Meaning ◽  
Increased Risk ◽  
Health Complications ◽  
Developed World

Perhaps no disease of pregnancy has been more thoroughly studied than pre-eclampsia (PE), and yet despite all of our efforts we are only beginning to understand the molecular mechanisms which underpin the disease. Many people are surprised by the frequency of PE in the population, as it is believed to occur in approximately one pregnancy out of 20 in the United States, with similar rates throughout the developed world. In severe cases the disorder can progress to eclampsia, which is characterized by maternal seizures and can lead to death. PE can only be treated by ending the pregnancy, often by inducing labour prior to term, making PE a leading cause of premature birth and all of the associated health complications which accompany it. All in all, PE is one of the leading causes of maternal and fetal morbidity and mortality. It is now also becoming apparent that PE disposes both the mother and the baby to increased risk of cardiovascular disease throughout life, meaning that we still don't fully understand the long-term implications of the disease.

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