Myo-inositol – A potential prophylaxis against premature onset of labour and preterm birth

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour-onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour-onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production, and secretion of pro-inflammatory chemocytokines, that overall dampen the pro-labour uteroplacental environment responsible for labour-onset and progress, thus, reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.

Dietary AGEs as Exogenous Boosters of Inflammation

Most chronic modern non-transmissible diseases seem to begin as the result of low-grade inflammation extending over prolonged periods of time. The importance of diet as a source of many pro-inflammatory compounds that could create and sustain such a low-grade inflammatory state cannot be ignored, particularly since we are constantly exposed to them during the day. The focus of this review is on specific components of the diet associated with inflammation, specifically advanced glycation end products (AGEs) that form during thermal processing of food. AGEs are also generated in the body in normal physiology and are widely recognized as increased in diabetes, but many people are unaware of the potential importance of exogenous AGEs ingested in food. We review experimental models, epidemiologic data, and small clinical trials that suggest an important association between dietary intake of these compounds and development of an inflammatory and pro-oxidative state that is conducive to chronic diseases. We compare dietary intake of AGEs with other widely known dietary patterns, such as the Mediterranean and the Dietary Approaches to Stop Hypertension (DASH) diets, as well as the Dietary Inflammation Index (DII). Finally, we delineate in detail the pathophysiological mechanisms induced by dietary AGEs, both direct (i.e., non-receptor-mediated) and indirect (receptor-mediated).

GLP-1 and Intestinal Diseases

Accumulating evidence implicates glucagon-like peptide-1 (GLP-1) to have, beyond glucose maintenance, a beneficial role in the gastrointestinal tract. Here, we review emerging data investigating GLP-1 as a novel treatment for intestinal diseases, including inflammatory bowel diseases, short-bowel syndrome, intestinal toxicities and coeliac disease. Possible beneficial mechanisms for these diseases include GLP-1′s influence on gastric emptying, its anti-inflammatory properties and its intestinotrophic effect. The current knowledge basis derives from the available GLP-1 agonist treatments in experimental animals and small clinical trials. However, new novel strategies including dual GLP-1/GLP-2 agonists are also in development for the treatment of intestinal diseases.

Immunomodulation as a Potent COVID-19 Pharmacotherapy: Past, Present and Future

In the first year of its appearance, the 2019 coronavirus disease (COVID-19) has affected more than 120 million individuals and killed 2 million people worldwide. The pandemic has also triggered numerous global initiatives to tackle the newly emerging disease, including the development of SARS-CoV-2 vaccines and the attempt to discover potential pharmacological therapies. Nonetheless, despite the success of SARS-CoV-2 vaccines development, the COVID-19 therapy remains challenging. Several repurposed drugs that were documented to be useful in small clinical trials have been shown to be ineffective in larger studies. Additionally, the pathophysiology of SARS-CoV-2 infection displayed the predominance of cytokine storm in inducing multiorgan damage. Therefore, the potential benefits of both immune modulation and suppression in COVID-19 have been extensively discussed. Here, we reviewed the roles of immunomodulation as potential COVID-19 pharmacological modalities based on the existing data and proposed several new immunologic targets to be tested in the foreseeable future.

On Frankincense (Olibanum, Boswellia spp., Burseraceae)

Boswellia species (Burseraceae) are trees or shrubs whose area of distribution covers the wide geographic area between North Africa and India. After incision, their bark produces oleogum resin known as frankincense (Olibanum). In traditional medicine, frankincense is often used for medical treatment of arthritis, asthma, ulcerative colitis, coughs, sores, and wound healing. Various frankincense preparations are marketed almost exclusively as dietary supplements. Indian frankincense, or Olibanum indicum, is official in the European Pharmacopoeia. The major components of frankincense are boswellic acids, among which the most important and abundant is 3-O-acetyl-11-keto-b-boswellic acid (AKBA). AKBA is a 5-lipoxygenase inhibitor with anti-inflammatory and anti-arthritic effects. Besides, frankincense contains essential oil, whose composition greatly depends on the biological source, as well as arabinogalactans and glycoproteins. In small clinical trials, certain benefits of various frankincense preparations have been demonstrated in cases of ulcerative colitis, bronchial asthma, mild symptoms of irritable bowel syndrome, and various disorders of osteo-muscular system. However, for collagenous colitis and Crohn's disease remission maintenance, the evidence is ambiguous or negative. AKBA-containing extract was found advantageous in patients with osteoarthritis, and to some extent with rheumatoid arthritis. Almost all the trials had serious flaws in experimental design, such as insufficient sample size and/or incomplete reporting of data. For any clinical recommendation of frankincense preparations, larger and better-designed studies are needed.

Anti-CD20 Agents for Multiple Sclerosis: Spotlight on Ocrelizumab and Ofatumumab

Until recently, in the pathogenesis of Multiple Sclerosis (MS), the contribution of B cells has been largely underestimated, and the disease was considered a T-cell-mediated disorder. However, newer evidence shows that B cells play a crucial role in the pathogenesis of MS via antigen-driven autoantibody responses and through the cross regulation of T-helper cells. As B cells express the surface molecule CD20 at all points of differentiation, it provides a specific target for monoclonal antibodies, and the development and clinical testing of anti-CD20 antibody treatments for MS have been successful. After some observations, some small clinical trials found positive effects for the first anti-CD20 therapeutic rituximab in MS; newer agents have been specifically evaluated, resulting in the development of ocrelizumab and ofatumumab. Ocrelizumab, a humanized anti-CD20 monoclonal antibody, was approved in March 2017 by the Food and Drug Administration (FDA) and is also the first proven therapy to reduce disability progression in primary progressive MS. This is particularly significant considering that disease-modifying treatment options are few for both primary and secondary progressive MS. Ofatumumab, a fully human anti-CD20 monoclonal antibody, that binds a distinct epitope, has been further investigated in phase 3 trials for relapsing forms of MS. In this review, we discuss in detail these two anti-CD20 agents and their advent for treatment of MS.

Chloroquine and Hydroxychloroquine in Treatment of Coronavirus Disease-19

At present, we are facing coronavirus disease (COVID)-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 with several treatment choices and reports of different treatment outcomes. Chloroquine and hydroxychloroquine use for the management of severely ill patients started as a quite enthusiastic treatment option, following several small clinical trials, case series reports, public authorities, and media affirmation. However, the evidence we have so far is conflicting and some national societies and professional institutions implicate that we should wait for definite treatment recommendations until there are solid data for or against the use of these drugs. Until we have more powerful evidence in our hands, we should be aware of safety issues of the old drugs for the new application in the emergency state we are facing today with the COVID-19 pandemic. We performed a concise review of strengths, limitations, and awareness for chloroquine and hydroxychloroquine use for COVID-19 infection treatment based on the evidence the science has today.

Is “Leptin Resistance” Another Key Resistance to Manage Type 2 Diabetes?

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Novel treatments for progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy is a rare demyelinating disorder of the CNS, caused by John Cunningham virus, that occurs in those with impaired immune systems. Existing treatment options are ineffective or unproven. This article reviews research into novel therapies: immune checkpoint-blocking antibodies (nivolumab and pembrolizumab), allogenic BK virus-specific T cell treatment and filgrastim. Results for these therapies in small clinical trials are promising, but further research is required to assess efficacy fully.