Why osteoarthritis of the knee is called "a wound that does not heal" and why Tai Chi is an effective treatment.

Context: Osteoarthritis (OA) of the knee is common and is associated with other chronic diseases and early mortality. OA is often described as a "wound that does not heal" because a local innate immune response gets dysregulated. Tai Chi is an aerobic mind-body practice that is recommended in national and international clinical practice guidelines as a treatment for OA of the knee. This review addressed two questions: What causes immune dysregulation in the knee? and Why is Tai Chi an effective treatment? Recent findings: There is now a good understanding of what causes OA of the knee at the cellular level. OA begins in the synovium from a phenotypic shift in synovial macrophages in response to tissue damage. The synovial macrophages release inflammatory cytokines, as part of the first phase of the normal healing and repair process. Cytokines communicate to other cells that there has been damage. This stimulates chondrocytes, osteoblasts, and fibroblasts to release inflammatory cytokines as well. When tissue damage is repetitive, there is repetitive release of inflammatory cytokines, and the normal healing process stops. The most common cause of tissue damage is from abnormal biomechanical forces on the knee that arise from trauma, injury, and misalignment. Tissue damage is made worse when there is systemic low-grade inflammation associated with other chronic conditions. Pain and stiffness often result in decreased physical activity, which leads to muscle weakness, progressive instability of the joint, and an increased risk of falls, further injuring the knee. Tai Chi improves alignment, optimizes the biomechanical forces on the knee, strengthens the lower limbs, and decreases systemic inflammation. Tai Chi improves balance and decreases the risk of falls and further injury. There is clinical and experimental evidence to suggest that by removing the causes of cell dysregulation, Tai Chi enables the normal healing and repair process to resume. Conclusion: Knee OA is a wound that does not heal primarily because repetitive adverse forces on the knee cause synovial macrophages and then local chondrocytes, osteocytes and fibroblasts to dysregulate and stop the normal healing and repair process. Tai Chi mitigates adverse forces on the knee and stabilizes the joint, creating the conditions whereby the normal healing and repair process can resume. Further research is needed.

Acupuncture as multi-targeted therapy for the multifactorial disease obesity: a complex neuro-endocrine-immune interplay.

The prevalence of obesity has reached pandemic dimensions. It is associated with multiple comorbidities and is becoming a clinical and public health threat. Obesity is a multifactorial disease with a complex pathophysiology and interplay of various systems. A strong interplay exists between the neuro-endocrine system, the immune system with systemic chronic low-grade inflammation, and microbiome dysbiosis that can lead to the development of obesity, which in turn can exacerbate each of these factors, hence creating a vicious cycle. The conventional treatment with lifestyle modifications such as diet, physical exercise, pharmacotherapy, and bariatric surgery does not always result in sufficient weight control thus paving the way for other strategies. As one such strategy, acupuncture is increasingly used worldwide to treat obesity. This narrative review outlines the evidence for this neuro-endocrine-immune interplay in the pathophysiology of obesity. Furthermore, the existing experimental and clinical evidence of acupuncture as a multi-targeted therapy for obesity is explained and future research perspectives are discussed.

Anthocyanin supplementation improves obesity-related inflammatory characteristics: A systematic review and meta-analysis of randomized controlled trials.

The relationship between anthocyanin intake and obesity-related inflammatory markers remains unclear in existing research. To investigate this, we hypothesized that anthocyanin supplementation could reduce plasma concentrations of inflammatory markers, including C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular cell adhesion molecule-1, and other cytokines in obesity. We conducted a systematic search of PubMed, Web of Science, Scopus, SinoMed, and other related literature and identified 16 randomized controlled trials that met our inclusion criteria. Our findings showed that anthocyanin intake was significantly associated with a reduction in vascular cell adhesion molecule-1 mean plasma concentrations (-53.56 ng/mL; 95% confidence interval [CI], -82.10 to -25.03). We also observed a modest decrease in CRP (-0.27 ng/mL; 95% CI, -0.58 to 0.05), TNF-α (-0.20 ng/mL; 95% CI, -0.54 to 0.15), and IL-6 (-0.53 ng/mL; 95% CI, -1.16 to 0.10) mean plasma concentrations. Subgroup analysis revealed that anthocyanin intake tended to decrease CRP and IL-6 concentrations in overweight or dyslipidemic individuals. Additionally, the intervention duration subgroup analysis showed that anthocyanin supplementation had a stronger effect on plasma IL-6 and TNF-α in participants after 8 to 12 weeks of intervention. In conclusion, our meta-analysis indicated that anthocyanin supplementation can effectively reduce obesity-related inflammatory markers associated with chronic low-grade inflammation.

Potential Modulation of Inflammation and Physical Function by Combined Probiotics, Omega-3 Supplementation and Vitamin D Supplementation in Overweight/Obese Patients with Chronic Low-Grade Inflammation: A Randomized, Placebo-Controlled Trial.

Obesity is characterized by low-grade inflammation and increased gut permeability. Here, we aim to evaluate the effect of a nutritional supplement on these parameters in subjects with overweight and obesity. A double-blinded, randomized clinical trial was conducted in 76 adults with overweight or obesity (BMI 28 to 40) and low-grade inflammation (high-sensitivity C-reactive protein (hs-CRP) between 2 and 10 mg/L). The intervention consisted of a daily intake of a multi-strain probiotic of Lactobacillus and Bifidobacterium, 640 mg of omega-3 fatty acids (n-3 FAs), and 200 IU of vitamin D (n = 37) or placebo (n = 39), administered for 8 weeks. hs-CRP levels did not change post-intervention, other than an unexpected slight increase observed in the treatment group. Interleukin (IL)-6 levels decreased in the treatment group (p = 0.018). The plasma fatty acid (FA) levels of the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio and n-6/n-3 ratio (p < 0.001) decreased, and physical function and mobility improved in the treatment group (p = 0.006). The results suggest that hs-CRP may not be the most useful inflammatory marker, but probiotics, n-3 FAs, and vitamin D, as non-pharmaceutical supplements, may exert modest effects on inflammation, plasma FA levels, and physical function in patients with overweight and obesity and associated low-grade inflammation.

Potential Modulation of Inflammation by Probiotic and Omega-3 Supplementation in Elderly with Chronic Low-Grade Inflammation-A Randomized, Placebo-Controlled Trial.

Probiotic and omega-3 supplements have been shown to reduce inflammation, and dual supplementation may have synergistic health effects. We investigated if the novel combination of a multi-strain probiotic (containing B. lactis Bi-07, L. paracasei Lpc-37, L. acidophilus NCFM, and B. lactis Bl-04) alongside omega-3 supplements reduces low-grade inflammation as measured by high-sensitivity C-reactive protein (hs-CRP) in elderly participants in a proof-of-concept, randomized, placebo-controlled, parallel study (NCT04126330). In this case, 76 community-dwelling elderly participants (median: 71.0 years; IQR: 68.0-73.8) underwent an intervention with the dual supplement (n = 37) or placebo (n = 39) for eight weeks. In addition to hs-CRP, cytokine levels and intestinal permeability were also assessed at baseline and after the eight-week intervention. No significant difference was seen for hs-CRP between the dual supplement group and placebo. However, interestingly, supplementation did result in significant increases in the level of the anti-inflammatory marker IL-10. In addition, dual supplementation increased levels of valeric acid, further suggesting the potential of the supplements in reducing inflammation and conferring health benefits. Together, the results suggest that probiotic and omega-3 dual supplementation exerts modest effects on inflammation and may have potential use as a non-pharmacological treatment for low-grade inflammation in the elderly.

The effects of local versus systemic passive heating on the acute inflammatory, vascular and glycaemic response.

The aim of this study was to compare the acute cardiometabolic and perceptual responses between local and whole-body passive heating. Using a water-perfused suit, 10 recreationally active males underwent three 90 min conditions: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and exposure to a thermoneutral temperature (CON). Blood samples were collected before and up to 3 h post-session to assess inflammatory markers, while a 2 h oral glucose tolerance test was initiated 1 h post-session. Femoral artery blood flow and perceptual responses were recorded at regular intervals. The interleukin (IL)-6 incremental area under the curve (iAUC) was higher for LBH (1096 ± 851 pg/mL × 270 min) and WBH (833 ± 476 pg/mL × 270 min) compared with CON (565 ± 325 pg/mL × 270 min; p < 0.047). Glucose concentrations were higher after WBH compared with LBH and CON (p < 0.046). Femoral artery blood flow was higher at the end of WBH (1713 ± 409 mL/min) compared with LBH (943 ± 349 mL/min; p < 0.001), and higher in LBH than CON (661 ± 222 mL/min; p = 0.002). Affect and thermal comfort were more negative during WBH compared with LBH and CON (p < 0.010). In conclusion, local passive heating elevated blood flow and the IL-6 iAUC. However, while resulting in more positive perceptual responses, the majority of the included cardiometabolic markers were attenuated compared with WBH. Novelty: The increase in the IL-6 iAUC in response to passive heating is not reduced by upper-body cooling. Upper-body cooling attenuates the plasma nitrite, IL-1ra and femoral artery blood flow response to passive heating. Upper-body cooling leads to more positive perceptual responses to passive heating.

Mean ± Standard Deviation Intake Values for 1-<10-Year-Old South African Children for Application in the Assessment of the Inflammatory Potential of Their Diets Using the DII® Method: Developmental Research.

This study aimed to develop a set of mean ± standard deviation (SD) intake values for South African (SA) children for 36 of the 45 food parameters included in the original Dietary Inflammatory Index (DII®) tool. The SA food composition database contains 30 of the 45 food parameters included in the original DII®, and a supplementary database was developed for six of the food parameters not included in the SA database. The SA child mean ± SD intake of macronutrients, micronutrients and select flavonoids was calculated by age in years, using eight data sets from dietary surveys conducted in SA in the last three decades. A total sample of 5412 children was included in the calculation of the mean ± SD. The current study sample was determined to be representative of 1-<10-year-old children in SA, and the plausibility of the mean intake values was confirmed by being in line with age-appropriate recommendations. Furthermore, an increase in energy, macronutrient, and most micronutrient intakes with increase in age was evident. The generated mean ± SD values for SA children can be used for calculation of the inflammatory potential of the dietary intake of SA children in the age range of 1-<10-year-old children.

Flavonoids from Scutellaria baicalensis inhibit senescence-associated secretory phenotype production by interrupting IκBζ/C/EBPß pathway: Inhibition of age-related inflammation.

BACKGROUND: Prolonged exposure to the senescence-associated secretory phenotype (SASP) with age leads to chronic low-grade inflammation in neighboring cells and tissues, causing many chronic degenerative diseases. PURPOSE: The effects on SASP production of the ethanol extract from Scutellaria radix and 17 isolated flavonoid constituents were examined in vitro and in vivo. METHODS: Cellular senescence was induced by bleomycin. Expression of the SASP and cell signaling molecules was detected using ELISA, RT-qPCR, Western blotting, and immunofluorescence staining. To investigate the in vivo effects, 21-month-old aged rats were used. RESULTS: The ethanol extract and 5 compounds including 1 (Oroxylin A; 5,7-dihydroxy-6-methoxyflavone), 5 (2',6',5,7-tetrahydroxy-8-methoxyflavone), 8 (2',5,7-trihydroxyflavone), 10 (2',5,7-trihydroxy-8-methoxyflavone) and 11 (2',5,7-trihydroxy-6-methoxyflavone) potently reduced IL-6 and IL-8 production and gene expression of the SASP, including IL-1α, IL-1ß, IL-6, IL-8, GM-CSF, CXCL1, MCP-2, and MMP-3. This finding indicates the important role of the B-ring 2'­hydroxyl group in flavonoid molecules. Furthermore, compounds 8 and 11, the strongest SASP inhibitors, decreased the expression of IκBζ and C/EBPß protein without affecting either BrdU uptake or the expression of senescence markers, such as pRb and p21. Finally, the oral administration of compound 8 to aged rats at 2 and 4 mg/kg/day for 10 days significantly inhibited the gene expression of SASP and IκBζ in kidneys. This is the first report of the strong SASP inhibitory action of flavonoids from Scutellaria radix on in vitro and in vivo senescence models. The inhibitory action was shown to be mediated mainly by interfering with the IκBζ/C/EBPß signaling pathway. CONCLUSION: Targeting production of the SASP using flavonoids from Scutellaria radix or its extract might help reduce low-grade sterile inflammation and control age-related diseases.

Supplementation of pyrroloquinoline quinone with atorvastatin augments mitochondrial biogenesis and attenuates low grade inflammation in obese rats.

Mitochondrial dysfunction and Inflammation play a significant role in the manifestation of the co-morbidities of obesity. The study deciphered the impact of Pyrroloquinoline quinone (PQQ) per se and with Atorvastatin (ATS) on high fat, 10% fructose diet (HFFD) induced obese rats expressing low-grade inflammation, dyslipidemia, and mitochondrial dysfunction. HFFD was fed for 10 weeks followed by treatment for 5 weeks with ATS 10 or 20 mg/kg, PQQ 10 or 20 mg/kg, p.o. per se or their combinations. The impact on blood glucose, lipid profile and serum insulin, TNF-α, IL-1ß, IL-18, IL-6 was estimated. Gene and protein expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC 1α), Sirtuin 1 (SIRT1), Mitochondrial transcriptional factor A (TFAM) and augmented mitochondrial DNA (mtDNA), NOD like receptor protein 3 (NLRP3) and Caspase 1 was assessed. Rats receiving PQQ and ATS revealed significant decrease in body weights, anthropometric parameter, and adipose tissue vis-à-vis positive control. PQQ alone and with ATS improved glucose tolerance, lipid profile, insulin indices and lowered serum levels of inflammatory cytokines IL-18, IL-1ß, TNF-α and IL-6 along with a rise in adiponectin. PQQ supplementation with ATS upregulated the mRNA expression of PGC 1α, SIRT1, TFAM and augmented mtDNA while downregulating inflammatory markers NLRP3 and Caspase 1. PQQ supplementation with atorvastatin holds therapeutic promise to effectively combat mitochondrial dysfunction and chronic low-grade inflammation in obesity.

Changing dynamics of psychoneuroimmunology during the COVID-19 pandemic.

The Coronavirus Disease-2019 (COVID-19) pandemic has led to a global health care crisis. Emerging research suggest an unanticipated impact of COVID-19 on mental and/or psychological health of both the general community and affected individuals. The fear of the COVID-19 epidemic and the consequent lockdown and economic crisis has led to globally increased psychological distress. The biological bases of immediate and new onset of psychiatric symptoms in individuals with COVID-19 are not yet known. COVID-19 infection may lead to activated immune-inflammatory pathways and a cytokine storm. Activated immune-inflammatory pathways, especially chronic low-grade inflammation, are associated with major psychiatric disorders in at least a subset of individuals. We propose that both the (sub)chronic inflammatory response and cytokine storm might crucially be involved in the immediate manifestation of neuropsychiatric symptoms in individuals with COVID-19 infection as well as heightened expression of psychiatric symptoms in COVID-19 infected individuals with prior psychiatric conditions. These events might expand concepts in psychoneuroimmunology, with the importance of chronic-low grade inflammation augmented by the cytokine storm hypothesis. Additionally, this might augment and refine diagnosis and prognostic management as well as treatment.

Acute and chronic effects of hot water immersion on inflammation and metabolism in sedentary, overweight adults.

Regular exercise-induced acute inflammatory responses are suggested to improve the inflammatory profile and insulin sensitivity. As body temperature elevations partly mediate this response, passive heating might be a viable tool to improve the inflammatory profile. This study investigated the acute and chronic effects of hot water immersion on inflammatory and metabolic markers. Ten sedentary, overweight men [body mass index (BMI): 31.0 ± 4.2 kg/m2, mean ± SD] were immersed in water set at 39°C for 1 h (HWI) or rested for 1 h at ambient temperature (AMB). Venous blood was obtained before the session, immediately postsession, and 2 h postsession for assessment of monocyte intracellular heat shock protein-72 (iHsp72) and plasma concentrations of extracellular Hsp72 (eHsp72), interleukin-6 (IL-6), fasting glucose, insulin, and nitrite. Thereafter, participants underwent a 2-wk intervention period, consisting of 10 hot water immersion sessions (INT). Eight BMI-matched participants (BMI: 30.0 ± 2.5 kg/m2) were included as control (CON). Plasma IL-6 and nitrite concentrations were higher immediately following HWI compared with AMB (IL-6 P < 0.001, HWI: 1.37 ± 0.94 to 2.51 ± 1.49 pg/ml; nitrite P = 0.04, HWI: 271 ± 52 to 391 ± 72 nM), whereas iHsp72 expression was unchanged ( P = 0.57). In contrast to resting iHsp72 expression ( P = 0.59), fasting glucose ( P = 0.04; INT: 4.44 ± 0.93 to 3.98 ± 0.98 mmol/l), insulin ( P = 0.04; INT: 68.1 ± 44.6 to 55.0 ± 29.9 pmol/l), and eHsp72 ( P = 0.03; INT: 17 ± 41% reduction) concentrations were lowered after INT compared with CON. HWI induced an acute inflammatory response and increased nitric oxide bioavailability. The reductions in fasting glucose and insulin concentrations following the chronic intervention suggest that hot water immersion may serve as a tool to improve glucose metabolism. NEW & NOTEWORTHY A single hot water immersion (HWI) session induces an acute increase in plasma interleukin-6 and nitrite concentrations but does not acutely elevate heat shock protein-72 expression in monocytes [intracellular Hsp72 (iHsp72)]. A chronic HWI intervention reduces fasting glucose and insulin concentrations in the absence of changes in resting iHsp72. Therefore, HWI shows potential as a strategy to combat chronic low-grade inflammation and improve glucose metabolism in individuals without the physical capacity to do so using exercise.

Causes and solutions to "globesity": The new fa(s)t alarming global epidemic.

Diverse groups of factors are leading to increased weight gain and obesity, such as certain genetic phenotypes, neuroendocrine disturbances, the administration of some drugs, behavioral, social and environmental factors. The progressively escalating rates of overweight and obesity worldwide have led to an introduction of a new term "globesity". Excessive accumulation of body fat and especially of visceral adipose tissue is the main predisposing factor for the development of metabolic syndrome and other obesity related co-morbidities. At the present moment only few pharmacotherapeuticals are used for long-term treatment of obesity acting on narrow target spectra, e.g. pancreatic and gastric lipase inhibition, acting as adrenomimetics or activating the satiety centers in hypothalamus. Plant-based medications that accelerate weight loss, proved to be safe, effective and widely available, would be a preferable alternative for anti-obesity treatments. As plant extracts are multi-component systems they could also act by more than one mechanism, including decreased lipid absorption, decreased energy intake, increased energy expenditure, decreased pre-adipocyte differentiation and proliferation, decreased lipogenesis and increased lipolysis. The current review gives a summary of the risk factors for obesity development and its characteristics consequences. Current treatment options, combining lifestyle changes and conventional treatment with commercial anti-obesity drugs have been described as well. Special emphasis on in vitro, in vivo and human studies, of potential medicinal plant extracts and phytochemicals, such as polyphenols, terpenoids, alkaloids, saponins, able to modulate the molecular pathways and gene/protein expressions related to obesity, have been highlighted.

A Brief Review of Blue- and Bilberries' Potential to Curb Cardio-Metabolic Perturbations: Focus on Diabetes.

Some epidemiological studies suggest that increased consumption of anthocyanins is associated with lower risk of cardiovascular disease (CVD) and hypertension. Also, high consumption of anthocyanin-rich fruit, such as berries, is associated with a lower risk of developing type 2 diabetes (T2D). In this review, we briefly yet critically assess the available evidence in support of an anti-diabetic role of anthocyanins derived from berries, especially bilberry (Vaccinium myrtillus L., also known as European blueberry, whortleberry, huckleberry and blaeberry) and blueberry (Vaccinium corymbosum, native to the United States). Further, cellular and molecular mechanisms are discussed and the "pharma-nutrition" use of anthocyanin-based preparations for the prevention and treatment of T2D is examined. We conclude that animal and in vitro studies strongly indicate that bilberry and blueberry have the potential to ameliorate T2D and its cardio-metabolic outcomes. However, appropriate clinical trials are lacking and will eventually clarify whether these foods (either as such or formulated as nutraceuticals) might be added to the current pharma-nutritional armamentarium.

Regular consumption of Fiit-ns, a polyphenol extract from fruit and vegetables frequently consumed within the Mediterranean diet, improves metabolic ageing of obese volunteers: a randomized, double-blind, parallel trial.

Epidemiological studies suggest that metabolic ageing process of overweight and obese populations is associated with an increased risk of developing non-communicable diseases (NCDs). Inflammation, hyper-glycaemia, dyslipidemia and oxidative stress have been associated with early stages of NCDs development whereas cohort surveys have demonstrated health benefits of dietary polyphenols from various dietary sources to reverse such progress. Obese volunteers were included in a double-blind, randomized, parallel pilot trial where they received daily for a 12-week period 900 mg of a polyphenol-rich treatment extracted from fruit and vegetables frequently consumed within the Mediterranean diet. Anthropometric and blood parameters were assessed before and at the end of the intervention period. After 12 weeks, while the silhouette slimmed down, metabolic parameters were significantly improved and general satisfaction considerably ameliorated. These data suggest that over a 12-week period, the synergistic action of bioactives within the treatment improves metabolic ageing process and quality of life in obese volunteers.