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- Volume 30, Issue 39, 2023
Current Medicinal Chemistry - Volume 30, Issue 39, 2023
Volume 30, Issue 39, 2023
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SARS-CoV-2 Infection, Inflammation, Immunonutrition, and Pathogenesis of COVID-19
The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A bibliometrics analysis on author’s keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is “self-destroy and rebuild”, which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms’ clearance could be only a passive bystander response to this destroy-rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a few possible coping strategies to mitigate COVID-19, including vaccination, are discussed.
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LSINCT5: A Novel lncRNA in Cancers
Authors: Xinyan Qiu and Jinlan ChenBackground: Long chain non-coding RNAs (lncRNA) are a kind of transcript that is around 200 nucleotides long and can engage in life activities via epigenetic, transcriptional, and post-transcriptional regulation. One of the key members of lncRNAs, long stress-induced noncoding transcripts 5 (LSINCT5), is localized at Chr 5p and has been reported to be abnormally expressed in a range of cancers. We present a comprehensive review of LSINCT5's aberrant expression and regulatory mechanisms in malignant tumors. Methods: The included studies were retrieved and summarized through the PubMed database using the keywords “LSINCT5” and “Cancer” in detail. Results: LSINCT5 behaves as an oncogene and abundantly expresses in malignant tumorigenesis and progression. By sponging microRNAs (miRNA), interacting with proteins, participating in cellular transduction, and being regulated by transcription factors, LSINCT5 can stimulate malignant behavior in a variety of tumor cells, including proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, dysregulated LSINCT5 is usually associated with a poor prognosis. Conclusion: LSINCT5 has the potential to become a tumor diagnostic and prognostic marker, generating new access to clinical applications.
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The Protective Effects of Silymarin on the Reproductive Toxicity: A Comprehensive Review
The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed.
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Extracellular Vesicles Derived from Plasmodium-infected Hosts as Stimuli of “Trained” Innate Immunity
Authors: Jin-Guang Chen, Yun-Ting Du, Chang-Hui Guan, Hua-Yu Fan, Yang-Ai Liu, Ting Wang, Xin Li and Guang ChenAlthough the burden of malaria has been successfully controlled globally, this disease remains a major public health issue. To date, neither existing drugs nor vaccines against malaria are sufficient in eliminating malaria worldwide. To achieve the eradication of malaria by 2040, effective interventions targeting all Plasmodium species are urgently needed. As the cornerstone of vaccine design, immune memory serves a significant role in the host's defense against Plasmodium infections. It has long been considered that innate immunity is non-specific and lacks immunologic memory. However, emerging evidence has suggested that innate immunity can be trained following exposure of the body to infectious agents, such as Plasmodium or its products, which, in turn, promotes the onset of a type of memory in innate immune cells. The above “trained” innate immune cells, whose phenotype is modified in response to epigenetic modifications, metabolic recombination, or cytokine secretion, exhibit differential pathophysiology after the exposure of the body to a pathogen. In addition, Plasmodium-infected red blood cells and other host cells can secrete exosomes that contain conserved parasite-specific information, such as proteins, RNA, non-coding RNA molecules, and nucleic acids. These molecules can act as stimuli for promoting the establishment of “trained” innate immunity against malaria, thereby altering the onset and progression of the parasitic disease. A deeper understanding of the role of exosomes in the development of “trained” innate immunity during Plasmodium infection could provide novel therapeutic and prevention strategies against malaria infections.
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Is BMI Associated with COVID-19 Severity? A Retrospective Observational Study
Background: Coronavirus-19 disease (COVID-19) is an infection with high morbidity and mortality. Obesity and low body mass index (BMI) have both been linked to severe COVID-19, but recent studies have failed to confirm these associations. Objectives: The aim of this study was to examine the relationship between BMI and disease progression in hospitalised patients with COVID-19. Methods: We performed a monocentric, retrospective observational study at the Fondazione Policlinico Gemelli in Rome. We enrolled 1544 (977 men) patients who presented to the emergency department with a positive COVID-19 test between January and December 2021. We divided patients into five classes based on BMI. Demographic, clinical, laboratory, and radiological data were collected for all patients. Results: Of the 1544 patients, 1297 recovered after hospitalization, whereas 247 (16%) died. Of those who died, 16/247 (6.5%) had a BMI below18.5 kg/m2, 72/247 (29%) had a BMI between 18.5 and 24.99 kg/m2, 103/247 (42%) had a BMI between 25 and 29.99 kg/m2, 36/247 (15%) had a BMI between 30 and 35 kg/m2, and 20/247 (8%) had a BMI above 35 kg/m2. After adjusting the results for age, sex, and concomitant diseases using multivariate logistic regression, we found a significantly increased risk of intensive care unit (ICU) admission in severely obese patients (BMI > 35) compared to normal weight patients (BMI: 18.5-24.99) (p > 0.001). Mortality was not associated with BMI. Conclusion: We confirm that severe obesity is a risk factor for ICU admission in patients with COVID-19. No association was found between BMI and mortality.
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The Derivatives of Cromolyn Ameliorate the Abnormal Misfolding of Amyloid Proteins and Neuroinflammation in the Neural Cells
Background: The representative symptom of Alzheimer’s Disease (AD) has mainly been mentioned to be misfolding of amyloid proteins, such as amyloid-beta (Aβ) and tau protein. In addition, the neurological pathology related to neuroinflammatory signaling has recently been raised as an important feature in AD. Currently, numerous drug candidates continue to be investigated to reduce symptoms of AD, including amyloid proteins misfolding and neuroinflammation. Objective: Our research aimed to identify the anti-AD effects of two chemical derivatives modified from cromoglicic acid, CNU 010 and CNU 011. Methods: CNU 010 and CNU 011 derived from cromoglicic acid were synthesized. The inhibitory effects of Aβ and tau were identified by thioflavin T assay. Moreover, western blots were conducted with derivates CNU 010 and CNU 011 to confirm the effects on inflammation. Results: CNU 010 and CNU 011 significantly inhibited the aggregation of Aβ and tau proteins. Moreover, they reduced the expression levels of mitogen-activated protein (MAP) kinase and nuclear factor kappa-light-chain-enhancer of activated B cells (NF- ΚB) signaling proteins, which are representative early inflammatory signaling markers. Also, the inhibitory effects on the lipopolysaccharide (LPS)-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) expression referring to late inflammation were confirmed. Conclusion: Our results showing multiple beneficial effects of cromolyn derivatives against abnormal aggregation of amyloid proteins and neuroinflammatory signaling provide evidence that CNU 010 and CNU 011 could be further developed as potential drug candidates for AD treatment.
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Changes of Colon in Rats with Different Ages in Response to Lipopolysaccharide
Authors: Yanli Li, Yuhui Guo, Liu Aoqi, Chengquan Ma, Zhengguo Xiong, Ding Yuan, Changcheng Zhang, Jihong Zhang and Yaoyan DunBackground: Lipopolysaccharide (LPS) is an endotoxin that causes inflammation, and the content of LPS increases gradually during the process of aging. Whether the response of the colon to LPS stimulation will increase with age is yet unknown. Objective: The study investigated the effects of LPS stimulation on the colon of adult and aging rats. Method: 43 healthy male SD rats were divided into 4 different groups: adult group and LPS-stimulated adult group at the age of 4 months, and aging group and LPS-stimulated aging group at the age of 22 months. Rats were stimulated by intraperitoneal injection of LPS (1mg/kg) for 24 h. The morphological changes of the colon were observed, and intestinal inflammatory response, tight junction proteins, apoptosis, and proliferation in intestinal epithelial cells were detected. Results: A series of morphology changes occurred in the colon of adult rats after LPS stimulation, the higher inflammatory response (TLR4, NF-ΚB, and IL-1β), changes in the protein levels of tight junctions (ZO-1, Claudin1, and Claudin2), and increased apoptosis (Bax, Bcl2) and proliferation (PCNA) of intestinal epithelial cells. The above changes were also found in aging rats. LPS stimulation further promotes the above changes to some extent in the colon of aging rats. Conclusion: A series of colon changes in rats was significantly damaged during LPS stimulation and aging, and these changes were further aggravated to some extent in LPS-stimulated aging rats.
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Volumes & issues
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Volume 32 (2025)
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Volume 31 (2024)
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Volume 30 (2023)
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Volume 29 (2022)
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Volume 28 (2021)
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Volume 27 (2020)
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Volume 26 (2019)
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Volume 25 (2018)
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Volume 24 (2017)
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Volume 23 (2016)
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Volume 22 (2015)
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Volume 21 (2014)
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Volume 20 (2013)
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Volume 19 (2012)
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Volume 18 (2011)
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Volume 17 (2010)
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Volume 16 (2009)
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Volume 15 (2008)
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Volume 14 (2007)
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Volume 13 (2006)
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Volume 12 (2005)
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Volume 11 (2004)
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Volume 10 (2003)
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Volume 9 (2002)
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Volume 8 (2001)
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Volume 7 (2000)