Rejected

Obesity-induced metabolic syndrome is a rapidly growing conundrum, reaching epidemic proportions globally. Chronic inflammation in obese adipose tissue plays a key role in metabolic syndrome with a series of local and systemic effects such as inflammatory cell infiltration and inflammatory cytokine secretion. Adipose tissue macrophages (ATM), as one of the main regulators in this process, are particularly crucial for pharmacological studies on obesity-related metabolic syndrome. Ponatinib, a multi-targeted tyrosine kinase inhibitor originally used to treat leukemia, has recently been found to improve dyslipidemia and atherosclerosis, suggesting that it may have profound effect on metabolic syndrome, although the mechanisms underlying have not yet been revealed. Here we discovered that ponatinib significantly improved insulin sensitivity in leptin deficient obese mice. In addition to that, ponatinib treatment remarkably ameliorated high fat diet-induced hyperlipidemia and inhibited ectopic lipid deposition in the liver. Interestingly, although ponatinib did not reduce but increase the weight of white adipose tissue (WAT), it remarkably suppressed the inflammatory response in WAT and preserved its function. Mechanistically, we showed that ponatinib had no direct effect on hepatocyte or adipocyte but attenuated free fatty acid (FFA) induced macrophage transformation from pro-inflammatory to anti-inflammatory phenotype. Moreover, adipocytes co-cultured with FFA-treated macrophages exhibited insulin resistance, while pre-treat these macrophages with ponatinib can ameliorate this process. These results suggested that the beneficial effects of ponatinib on metabolic disorders are achieved by inhibiting the inflammatory phenotypic transformation of ATMs, thereby maintaining the physiological function of adipose tissue under excessive obesity. The data here not only revealed the novel therapeutic function of ponatinib, but also provided a theoretical basis for the application of multi-target tyrosine kinase inhibitors in metabolic diseases.

Advances in spinal cord stimulator (SCS) technology and increasing prevalence of magnetic resonance imaging (MRI) diagnostic testing require empirical evidence describing the presence of MRI-related SCS adverse events related to off-label use of imaging. MRI safety recommendations vary based on the type of stimulator used with scant availability regarding adverse events associated with off-label MRI use. The aim of this case series is to describe the type and frequency of adverse events associated with off-label MRI use in patients with implanted SCSs.

We report the introduction of a novel single-port laparoscopic-assisted trans-scrotal hernia sac ligation (LAT-HSL) technique for the treatment of inguinal hernias in pediatric males. In this article, we describe the LAT-HSL technique and the outcomes.

Previous in vitro and in vivo studies indicated that walnut extract has a therapeutic effect on herpes simplex infections. This study aimed to evaluate the efficacy and tolerance of Lazolex® Gel (Iveriapharma, Tbilisi, Georgia), an emollient gel to treat mucocutaneous lesions caused by herpes simplex virus.

Genomic screening is an informative and helpful tool for the clinical management of inherited conditions such as cardiac diseases. Cardiac-inherited diseases are a group of disorders affecting the heart, its system, function, and vasculature. Among the cardiac inherited abnormalities, one of the most common is Wolff-Parkinson-White syndrome. Similarly, hypertrophic cardiomyopathy is another common autosomal dominant inherited cardiac disease. Hypertrophic cardiomyopathy is associated with an increased incidence of Wolff-Parkinson-White syndrome; reports have suggested that it could be caused by a mutation in the protein-coding gene PRKAG2, which encodes a subunit of the AMP-activated protein kinase.

Diabetic foot ulcers (DFUs) have a significant impact on a patient's quality of life and life expectancy, with mortality rates comparable with malignant diseases. However, there is a lack of data regarding palliative care needs in this population. We aimed to characterize palliative care needs in people under diabetic foot surveillance using the Integrated Palliative care Outcome Scale (IPOS) and EuroQol-5D three-level version (EQ-5D-3L) and to assess differences between those with and without a DFU.

Neuropathic pain (NP) is expected to increase due to the high risk of global population aging. Acupuncture has a definite clinical effect on NP. Therefore, a systematic review and meta-analysis were conducted to evaluate the effect on pain intensity and safety of acupuncture in patients with NP.

Long-COVID is a syndrome characterized by debilitating symptoms that persist over 3 months after infection with the SARS-CoV-2 virus. It affects 15 to 33% of COVID-19 recovered patients and has no dedicated treatment. First, we found that β-caryophyllene and pregnenolone have a significant synergistic effect in the resolution of LPS-induced sepsis and inflammation in mice. Then we combined these two compounds with seven others and designed a unique dietary supplement formulation to alleviate long COVID inflammatory and neurological disorders. We performed a one-arm open-labeled study at a single site with 51 eligible patients from 18 states. Each participant recorded the severity level of 12 symptoms (including fatigue, weakness, cardiac and neurological symptoms, shortness of breath, gastrointestinal disorders, ageusia or anosmia, anxiety, joint pain, rash, cough, and insomnia) at baseline, 2- and 4-week time points. On average, all the symptoms were significantly milder after 2 weeks, with further improvement after 4 weeks. Importantly, each symptom was significantly attenuated in 72 to 84% of the participants. There were no significant adverse effects. Our data indicate that the use of this nutraceutical product is a safe and significantly efficient option to reduce multiple symptoms of long COVID.

is one of the herbal products with anti-inflammatory, antioxidant, moisturizing, bactericidal, anti-viral, and anti-fungal effects that were used to relieve pain and irritation. The aim of the current systematic review and meta-analysis is to determine the effect of on the relief of irritation and nipple pain in lactating women.

Cerebrovascular involvement of Kawasaki disease (KD) is poorly studied. White matter hyperintensities (WMH) indicate cerebral small vessel disease and increase the risk for stroke.