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Corona virus disease 2019 (COVID‐19) causes symptoms from multiple organs after infection by severe acute respiratory syndrome corona virus 2 (SARS CoV‐2). They range from early, low blood oxygen levels (hypoxemia) without breathlessness (“silent hypoxia”), delirium, rashes, and loss of smell (anosmia), to persisting chest pain, muscle weakness and ‐pain, fatigue, confusion, memory problems and difficulty to concentrate (“brain fog”), mood changes, and unexpected onset of hypertension or diabetes. SARS CoV‐2 affects the microcirculation, causing endothelial cell swelling and damage (endotheliitis), microscopic blood clots (microthrombosis), capillary congestion, and damage to pericytes that are integral to capillary integrity and barrier function, tissue repair (angiogenesis), and scar formation. Similar to other instances of critical illness, COVID‐19 is also associated with elevated cytokine levels in the systemic circulation. This review examines how capillary damage and inflammation may contribute to these acute and persisting COVID‐19 symptoms by interfering with blood and tissue oxygenation and with brain function. Undetectable by current diagnostic methods, capillary flow disturbances limit oxygen diffusion exchange in lungs and tissue and may therefore cause hypoxemia and tissue hypoxia. The review analyzes the combined effects of COVID‐19‐related capillary damage, pre‐existing microvascular changes, and upstream vascular tone on tissue oxygenation in key organs. It identifies a vicious cycle, as infection‐ and hypoxia‐related inflammation cause capillary function to deteriorate, which in turn accelerates hypoxia‐related inflammation and tissue damage. Finally, the review addresses the effects of low oxygen and high cytokine levels in brain tissue on neurotransmitter synthesis and mood. Methods to assess capillary functions in human organs and therapeutic means to protect capillary functions and stimulate capillary bed repair may prove important for the individualized management of COVID‐19 patients and targeted rehabilitation strategies. COVID‐19‐related microvascular damage and inflammation may cause tissue hypoxia via transit‐time effects and disturb neurotransmitter synthesis in the brain. The duration of COVID‐19 symptoms and the long‐term health effects of SARS‐CoV‐2 infection may rely on whether disease‐related capillary damage is reversible.

During postnatal development, colostrum and breastmilk are sequentially the first sources of nutrition with protein components and bioactive molecules that confer protection and immunostimulatory function to the gut. Caseins, whey proteins, secretory immunoglobulin A (sIgA), mucins, tryptophan, and growth factors are among milk‐borne elements that are directly important in the control of mucosa development and protection. Consequently, breastfeeding is associated with the low incidence of gastrointestinal inflammation and with the decrease in respiratory diseases during postnatal period. The novel coronavirus (SARS‐CoV‐2) binds to angiotensin II‐converting enzyme (ACE2) on the cell membrane, allowing virus entrance, replication, and host commitment. ACE2 is expressed by different cell types, which include ciliated cells in the lungs and enterocytes in the intestine. Such cells are highly active in metabolism, as they internalize molecules to be processed and used by the organism. The disruption of ACE2 impairs leads to intestinal inflammation and decreased synthesis of serotonin, affecting motility. By reviewing the effects of SARS‐CoV‐2 in the gastrointestinal and respiratory tracts in infants, and gut responses to breastfeeding interruption, we suggest that it is important to maintain breastfeeding during SARS‐CoV‐2 infection, as it might be essential to protect newborns from gastrointestinal‐associated disorders and relieve disease symptoms. We currently reviewed the effects of SARS‐CoV‐2 in the gastrointestinal and respiratory tracts in infants and discussed gut responses to breastfeeding interruption, and we suggest that it is important to maintain breastfeeding during SARS‐CoV‐2 infection, as it might be essential to protect newborns from gastrointestinal‐associated disorders and relieve disease symptoms.

Purpose There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective. Methods A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed. Results The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3 mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender–dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements. Conclusion Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.

Crush syndrome is characterized by ischemia/reperfusion injury (IRI). The protective effect of nitrite on experimentally induced IRI has been demonstrated in the heart, kidney, liver, and skeletal muscle. IRI in tissues and systemic organs occurs due to the massive generation of reactive oxygen species and subsequent systemic inflammation. Therefore, ischemic pre and postconditioning are performed in clinical practice. Intravenous administration of nitrite inhibits IRI through nitric oxide‐mediated mechanisms. In this paper, we discuss the utility of nitrite as a pharmacological postconditioning agent in the treatment of crush syndrome. This study summarizes research findings on the pharmacological benefits of nitrite in the treatment of crush syndrome. We discuss a possibility for nitrite to be used for the treatment of crush syndrome as a pharmacological postconditioning agent.

The global spread of COVID-19 has raised the importance of pharmaceutical drug development as intractable and hot research. Developing new drug molecules to overcome any disease is a costly and lengthy process, but the process continues uninterrupted. The critical point to consider the drug design is to use the available data resources and to find new and novel leads. Once the drug target is identified, several interdisciplinary areas work together with artificial intelligence (AI) and machine learning (ML) methods to get enriched drugs. These AI and ML methods are applied in every step of the computer-aided drug design, and integrating these AI and ML methods results in a high success rate of hit compounds. In addition, this AI and ML integration with high-dimension data and its powerful capacity have taken a step forward. Clinical trials output prediction through the AI/ML integrated models could further decrease the clinical trials cost by also improving the success rate. Through this review, we discuss the backend of AI and ML methods in supporting the computer-aided drug design, along with its challenge and opportunity for the pharmaceutical industry.Graphic abstractFrom the available information or data, the AI and ML based prediction for the high throughput virtual screening. After this integration of AI and ML, the success rate of hit identification has gained a momentum with huge success by providing novel drugs.

Background Metastatic cells from a primary tumor can occur before the primary cancer is detected. Metastatic cells can also remain in the patient for many years after removal of the primary tumor without proliferating. These dormant malignant cells can awaken and cause recurrent disease decades after the primary treatment. The purpose of this article is to review the clinical evidence for early dissemination and late recurrences in human malignant tumors. We used the following definitions: dormancy of cells may be defined as a nonproliferating state or an arrest in the cell cycle that results in a prolonged G0 phase. If one accepts the term “late metastases” to indicate a period exceeding 10 years from the removal of the primary tumor, then the two malignancies in which this occurs most frequently are cutaneous malignant melanoma (CMM) and renal cell carcinoma (RCC). Methods PubMed, Web of Science, and Scopus were searched with the keywords “metastases,” “early dissemination,” “late recurrences,” “inadvertently transmitted cancer,” “tumor growth rate,” “dormancy,” “circulating tumor cells,” and “transplantation of cancer.” Results Several case reports of early dissemination and late recurrences of various types of malignancies were found. Analyses of the growth rates of several malignant tumors in the original host indicated that the majority of cancers had metastasized years before they were detected. CMM, RCC, and malignant glioblastoma were the three most common malignancies resulting from an organ transplantation. CMM and RCC were also the two most common malignancies that showed dormancy. In several cases of transplanted CMM and RCC, the donor did not have any known malignancy or had had the malignancy removed so long ago that the donor was regarded as cured. Conclusion (1) Metastases can frequently exist prior to the detection of the primary tumor. (2) Metastatic cells may reside in organs in the original host that are not usually the site of detectable secondary tumors, for example, the kidneys and heart. (3) Metastatic cells remain dormant for decades after the primary tumor has been removed. (4) Dormancy might be reversible and lead to late recurrences.

Transcriptome analysis of individual cells by single-cell RNA-seq (scRNA-seq) has become routine for eukaryotic tissues, even being applied to whole multicellular organisms. In contrast, developing methods to read the transcriptome of single bacterial cells has proven more challenging, despite a general perception of bacteria as much simpler than eukaryotes. Bacterial cells are harder to lyse, their RNA content is about two orders of magnitude lower than that of eukaryotic cells, and bacterial mRNAs are less stable than their eukaryotic counterparts. Most importantly, bacterial transcripts lack functional poly(A) tails, precluding simple adaptation of popular standard eukaryotic scRNA-seq protocols that come with the double advantage of specific mRNA amplification and concomitant depletion of rRNA. However, thanks to very recent breakthroughs in methodology, bacterial scRNA-seq is now feasible. This short review will discuss recently published bacterial scRNA-seq approaches (MATQ-seq, microSPLiT, and PETRI-seq) and a spatial transcriptomics approach based on multiplexed in situ hybridization (par-seqFISH). Together, these novel approaches will not only enable a new understanding of cell-to-cell variation in bacterial gene expression, they also promise a new microbiology by enabling high-resolution profiling of gene activity in complex microbial consortia such as the microbiome or pathogens as they invade, replicate, and persist in host tissue.

The discovery of nalidixic acid is one pinnacle in medicinal chemistry, which opened a new area of research that has led to the discovery of several life-saving antimicrobial agents (generally referred to as fluoroquinolones) for over decades. Although fluoroquinolones are frequently encountered in the literature, the utility of quinolone compounds extends far beyond the applications of fluoroquinolones. Quinolone-based compounds have been reported for activity against malaria, tuberculosis, fungal and helminth infections, etc. Hence, the quinolone scaffold is of great interest to several researchers in diverse disciplines. This article highlights the versatility of the quinolone pharmacophore as a therapeutic agent beyond the fluoroquinolone profile.

Insulin resistance is a prevalent syndrome in developed as well as developing countries. It is the predisposing factor for type 2 diabetes mellitus, the most common end stage development of metabolic syndrome in the United States. Previously, studies investigating type 2 diabetes have focused on beta cell dysfunction in the pancreas and insulin resistance, and developing ways to correct these dysfunctions. However, in recent years, there has been a profound interest in the role that oxidative stress in the peripheral tissues plays to induce insulin resistance. The objective of this review is to focus on the mechanism of oxidative species generation and its direct correlation to insulin resistance, to discuss the role of obesity in the pathophysiology of this phenomenon, and to explore the potential of antioxidants as treatments for metabolic dysfunction.

Purpose Environmental endocrine-disrupting chemicals (EDCs) are a mixture of chemical compounds capable to interfere with endocrine axis at different levels and to which population is daily exposed. This paper aims to review the relationship between EDCs and breast, prostate, testicle, ovary, and thyroid cancer, discussing carcinogenic activity of known EDCs, while evaluating the impact on public health. Methods A literature review regarding EDCs and cancer was carried out with particular interest on meta-analysis and human studies. Results The definition of EDCs has been changed through years, and currently there are no common criteria to test new chemicals to clarify their possible carcinogenic activity. Moreover, it is difficult to assess the full impact of human exposure to EDCs because adverse effects develop latently and manifest at different ages, even if preclinical and clinical evidence suggest that developing fetus and neonates are most vulnerable to endocrine disruption. Conclusion EDCs represent a major environmental and health issue that has a role in cancer development. There are currently some EDCs that can be considered as carcinogenic, like dioxin and cadmium for breast and thyroid cancer; arsenic, asbestos, and dioxin for prostate cancer; and organochlorines/organohalogens for testicular cancer. New evidence supports the role of other EDCs as possible carcinogenic and pregnant women should avoid risk area and exposure. The relationship between EDCs and cancer supports the need for effective prevention policies increasing public awareness.