Rationale:A number of epidemiological studies have suggested an association of hyperhomocysteinemia (HHcy) and abdominal aortic aneurysm (AAA), but discrepancies exist. In addition, we lack direct evidence supporting a causal role. Objective:We determined the association and contribution of HHcy to AAA formation. Methods and Results:We first performed a meta-analysis of studies involving 1489 subjects and found a strong association of HHcy and AAA (odds ratio, 7.39). Next, we used angiotensin II–infused male apolipoprotein E–deficient mice and tested whether HHcy contributes to AAA pathogenesis. Homocysteine (Hcy) supplement (1.8 g/L) in drinking water resulted in mild HHcy. Intriguingly, HHcy greatly increased the incidence of angiotensin II–induced AAA and aortic dissection in apolipoprotein E–deficient mice (vehicle versus Hcy: 50% versus 100%; P<0.05). Histology indicated HHcy markedly exaggerated aortic adventitial inflammation. Increased levels of proinflammatory interleukin-6 and monocyte chemoattr...

Hyperhomocysteinemia Exaggerates Adventitial Inflammation and Angiotensin II−Induced Abdominal Aortic Aneurysm in Mice

Knee osteoarthritis (KOA) is a degenerative disease, making a unique contribution to chronic pain, edema, and limited mobility of knee joint. Traditional Chinese Medicine (TCM) is a common complementary therapy for KOA and has been found effective. The aim of this review is to consolidate the current knowledge about the mechanism of four interventions of TCM: acupuncture, moxibustion, herbs, and massage in treating KOA, and how they alleviate symptoms such as pain, swelling, and dysfunction. Furthermore, this review highlights that four therapies have different mechanisms but all of them can manage KOA through inhibiting inflammation, which indicates that alternative therapies should be considered as a viable complementary treatment for pain management in clinical practice.

/pdf/mechanism-of-traditional-chinese-medicine-in-treating-knee-41o2vkecsh.pdf

Mechanism of Traditional Chinese Medicine in Treating Knee Osteoarthritis

Nitric Oxide (NO) is a potent signaling molecule involved in the regulation of various cellular mechanisms and pathways under normal and pathological conditions. NO production, its effects, and its efficacy, are extremely sensitive to aging-related changes in the cells. Herein, we review the mechanisms of NO signaling in the cardiovascular system, central nervous system (CNS), reproduction system, as well as its effects on skin, kidneys, thyroid, muscles, and on the immune system during aging. The aging-related decline in NO levels and bioavailability is also discussed in this review. The decreased NO production by endothelial nitric oxide synthase (eNOS) was revealed in the aged cardiovascular system. In the CNS, the decline of the neuronal (n)NOS production of NO was related to the impairment of memory, sleep, and cognition. NO played an important role in the aging of oocytes and aged-induced erectile dysfunction. Aging downregulated NO signaling pathways in endothelial cells resulting in skin, kidney, thyroid, and muscle disorders. Putative therapeutic agents (natural/synthetic) affecting NO signaling mechanisms in the aging process are discussed in the present study. In summary, all of the studies reviewed demonstrate that NO plays a crucial role in the cellular aging processes.

https://www.mdpi.com/1420-3049/26/15/4533/pdf

An Overview of NO Signaling Pathways in Aging

There is a high level of interest in integrative strategies to augment public health measures to prevent COVID-19 infection and associated pneumonia. Unfortunately, no integrative measures have been validated in human trials as effective specifically for COVID-19. Notwithstanding, this is an opportune time to be proactive. Using available in-vitro evidence, an understanding of the virulence of COVID-19, as well as data from similar, but different, viruses, we offer the following strategies to consider. Again, we stress that these are supplemental considerations to the current recommendations that emphasize regular hand washing, physical distancing, stopping non-essential travel, and obtaining testing in the presence of symptoms. While the pathogenicity of COVID-19 is complex, it is important to understand the role of inflammation in this disease. The virulence and pathogenicity (including acute respiratory distress syndrome) associated with SARS corona viruses develops as the result of viral activation of cytoplasmic NLRP3 inflammasome. This inflammasome within activated (upregulated NFkB) macrophages and Th1 immune cells releases proinflammatory cytokines, namely IL-1B and IL-18, which dictate the pathogenic inflammation responsible for the virulence and symptoms of COVID-19. Understanding this component of COVID-19 infection provides a mechanistic underpinning to several of the following.

Integrative considerations during the COVID-19 pandemic.

UFL1 attenuates IL-1β-induced inflammatory response in human osteoarthritis chondrocytes.

Background: Osteoarthritis (OA) is a chronic joint-degeneration disease and accounts for the most frequent arthritis in aging people. OA is characterized by the degeneration of articular ca...

Astragaloside inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.

Background: Many studies have assessed the potential link between interleukin-6 polymorphisms and susceptibility to allergic diseases. However, the results are still conflicting. Therefore, a comprehensive meta-analysis can not only resolve differences but also provide clues for future projects. Methods: A systematic electronic search was conducted on the databases of Web of Science, PubMed, and Cochrane Library to retrieve all published studies. Revman and Stata software were used for statistical analysis. Results: This meta-analysis included 11 studies. The results revealed that there was a statistically significant association between IL-6 rs1800795 polymorphism and the risk of asthma and allergic rhinitis in the general population. Subgroup analyses demonstrated that rs1800795 affected allergic diseases risk in different populations. Conclusion: Our findings suggested that IL-6 rs1800795 was associated with allergic diseases susceptibility among Asians and Caucasians in opposite trends, and it might influence the risk of asthma and allergic rhinitis. None of the IL-6 polymorphisms were shared risk variants of allergic diseases.

/pdf/effects-of-il-6-polymorphisms-on-individual-susceptibility-1prz20mt.pdf

Effects of IL-6 Polymorphisms on Individual Susceptibility to Allergic Diseases: A Systematic Review and Meta-Analysis

The circadian clock is closely associated with inflammatory reactions. Increased inflammatory cytokine levels have been detected in the airways of nocturnal asthma. However, the mechanisms that contribute to the nocturnal increase in inflammatory responses and the relationship with circadian clock remain unknown. Methods Inflammatory cytokine levels were measured in asthma patients with and without nocturnal symptoms. Allergic airway disease was induced in mice by ovalbumin (OVA), and different periods of light/dark cycles were used to induce circadian rhythm disorders. Serum shock was used to stimulate the rhythmic expression in human bronchial epidermal cells (16HBE). The expression and oscillation of circadian clock genes and inflammatory cytokines in 16HBE cells subjected to brain and muscle ARNT-like protein-1 (BMAL1) and Forkhead Box A2 (FOXA2) knockdown and treatment with a FOXA2 overexpression plasmid were assessed. Results Serum IL-6 was found to be significantly higher in asthmatic patients with nocturnal symptoms than those without nocturnal symptoms. The OVA-induced asthma model with a circadian rhythm disorder and 16HBE cells treated with serum shock showed an increase in IL-6 levels and a negative correlation with BMAL1 and FOXA2. The knockdown of BMAL1 resulted in a lower correlation between IL-6 and other rhythm clock genes. Furthermore, knockdown of the BMAL1 and FOXA2 in 16HBE cells reduced the expression and rhythmic fluctuations of IL-6. Conclusions Our findings suggest that there are increased IL-6 levels in nocturnal asthma resulting from inhibition of the BMAL1/FOXA2 signalling pathway in airway epithelial cells.

/pdf/bmal1-foxa2-induced-rhythmic-fluctuations-in-il-6-contribute-1p14hrnp.pdf

BMAL1/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks

BMAL1 regulates MUC1 overexpression in ovalbumin-induced asthma.

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Astragaloside inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and ameliorates the progression of osteoarthritis in mice.

Effects of IL-6 Polymorphisms on Individual Susceptibility to Allergic Diseases: A Systematic Review and Meta-Analysis

BMAL1/FOXA2-induced rhythmic fluctuations in IL-6 contribute to nocturnal asthma attacks

BMAL1 regulates MUC1 overexpression in ovalbumin-induced asthma.