Rejected

Mn(III) -tetrakis(-ethylpyridinium-2-yl)porphyrin chloride (MnTE-2-PyPCl, BMX-010, and AEOL10113) is among the most studied superoxide dismutase (SOD) mimics and redox-active therapeutics, being currently tested as a drug candidate in a phase II clinical trial on atopic dermatitis and itch. The thermal stability of active pharmaceutical ingredients (API) is useful for estimating the expiration date and shelf life of pharmaceutical products under various storage and handling conditions. The thermal decomposition and kinetic parameters of MnTE-2-PyPCl were determined by thermogravimetry (TG) under nonisothermal and isothermal conditions. The first thermal degradation pathway affecting Mn-porphyrin structural integrity and, thus, activity and bioavailability was associated with loss of ethyl chloride via -dealkylation reaction. The thermal stability kinetics of the -dealkylation process leading to MnTE-2-PyPCl decomposition was investigated by using isoconversional models and artificial neural network. The new multilayer perceptron (MLP) artificial neural network approach allowed the simultaneous study of ten solid-state kinetic models and showed that MnTE-2-PyPCl degradation is better explained by a combination of various mechanisms, with major contributions from the contraction models R1 and R2. The calculated activation energy values from isothermal and nonisothermal data were about 90 kJ mol on average and agreed with one another. According to the R1 modelling of the isothermal decomposition data, the estimated shelf life value for 10% decomposition ( ) of MnTE-2-PyPCl at 25°C was approximately 17 years, which is consistent with the high solid-state stability of the compound. These results represent the first study on the solid-state decomposition kinetics of Mn(III) 2–alkylpyridylporphyrins, contributing to the development of this class of redox-active therapeutics and SOD mimics and providing supporting data to protocols on purification, handling, storage, formulation, expiration date, and general use of these compounds.

The aim was to develop a prediction model of sustained remission after cessation of biologic or targeted synthetic DMARD (b/tsDMARD) in RA.

There is a high incidence of alexithymia in people who report medically unexplained symptoms. There have been limited studies on the prevalence of alexithymia in patients with medically unexplained physical symptoms (MUPS) in various ethnic and cultural backgrounds.

Ulcerative colitis (UC) is a chronic non-specific inflammatory bowel disease, which usually manifests as abdominal pain, diarrhea and hematochezia. The disease often recurs and is difficult to cure. At present, the pathogenesis is not clear, but it is believed that the disease is caused by a complex interaction among immunity, heredity, environment and intestinal microflora disorders. MicroRNA (miRNA) is endogenous single-stranded non-coding RNA of 17-25 nucleotides (nts). They target the 3'Untranslated Region of a target gene and inhibit or degrade the target gene according to the extent of complementary bases. As important gene expression regulators, miRNAs are involved in regulating the expression of most human genes, and play an important role in the pathogenesis of many autoimmune diseases including UC. Studies in recent years have illustrated that abnormal expression of miRNA occurs very early in disease pathogenesis. Moreover, this abnormal expression is highly related to disease activity of UC and colitis-associated cancer, and involves virtually all key UC-related mechanisms, such as immunity and intestinal microbiota dysregulation. Recently, it was discovered that miRNA is highly stable outside the cell in the form of microvesicles, exosomes or apoptotic vesicles, which raises the possibility that miRNA may serve as a novel diagnostic marker for UC. In this review, we summarize the biosynthetic pathway and the function of miRNA, and summarize the usefulness of miRNA for diagnosis, monitoring and prognosis of UC. Then, we described four types of miRNAs involved in regulating the mechanisms of UC occurrence and development: 1) miRNAs are involved in regulating immune cells; 2) affect the intestinal epithelial cells barrier; 3) regulate the homeostasis between gut microbiota and the host; and 4) participate in the formation of tumor in UC. Altogether, we aim to emphasize the close relationship between miRNA and UC as well as to propose that the field has value for developing potential biomarkers as well as therapeutic targets for UC.

This study was designed to assess the levels of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in diabetes patients to determine their prognostic value in predicting the disease of diabetic peripheral neuropathy (DPN).

To establish the wound management property of a hydroethanolic leaf extract (CFHE).

To characterize the expression of long non-coding RNA LncRNA-FA2H-2 in coronary heart disease (CHD) and its correlation with inflammatory markers. From December 2018 to December 2020, 316 patients at Henan Provincial People's Hospital who complained of chest tightness or chest pain and had coronary angiography to clarify their coronary artery conditions for definitive diagnoses were selected as the study subjects. Plasma was collected to detect white blood cells (WBCs), total cholesterol (TG), triglyceride cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (ApoA1), and C-reactive protein (CRP) levels. Tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and interleukin-6 (IL-6) levels were also measured using ELISA. The expression levels of lncRNA-FA2H-2 were measured using quantitative real-time PCR. The data obtained were analyzed by independent sample -tests, rank sum tests, regression analyses, Pearson's or Spearman's correlation analyses, and receiver operating characteristic curves. (1) Compared with the control group, the differences in age, sex, diabetes, smoking, drinking, body mass index (BMI), WBC, TC, and LDL-C in CHD were not statistically significant, while the differences in hypertension, TG, HDL-C, ApoA1, and CRP were statistically significant. (2) In the grouping of coronary lesion branches, patients with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TC, LDL-C, HDL-C, and ApoA1 differences were not statistically significant, but TG and CRP differences were statistically significant. (3) The relative expressions of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 were significantly upregulated in the CHD group ( < 0.001). (4) The results showed that the relative levels of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. In addition, positive correlations were found between the Gensini score and TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD patients. (5) LncRNA-FA2H-2 relative expression in the CHD group was significantly downregulated ( < 0.001). (6) The differences in the expression levels of LncRNA-FA2H-2 were statistically significant between the two comparative analyses ( < 0.01), except between the 2-branch lesion and 3-branch lesion groups. (7) LncRNA-FA2H-2 was not associated with age, sex, hypertension, diabetes, smoking, drinking, BMI, WBC, TG, TC, LDL-C, HDL-C, and ApoA1 ( > 0.05). (8) A correlation was found between LncRNA-FA2H-2 and MCP-1, and VCAM-1, ICAM-1, IL-6, and Gensini. (9) The results indicated that the relative levels of LncRNA-FA2H-2 between the two comparative analyses (high risk, moderate risk, and low risk groups) were statistically significant. A negative correlation was found between the Gensini score and LncRNA-FA2H-2. (10) ROC curve analyses of TNF-α, MCP-1, VCAM-1, ICAM-1, and IL-6 in CHD showed the area under the curve (AUC) = 0.832 (0.77, 0.893) with a cut-off value of 290.5, a sensitivity of 73%, and a specificity of 64%; AUC = 0.731 (0.653, 0.809) with a cut-off value of 396 and with a sensitivity of 59% and specificity of 79%; AUC = 0.822 (0.757, 0.887) with a cut-off value of 264 and with a sensitivity of 72% and specificity of 83%; AUC = 0.794 (0.715, 0.874) with a cut-off value of 201.5 and with a sensitivity of 75% and specificity of 65%; AUC = 0.760 (0.685, 0.834) with a cut-off value of 328 and with a sensitivity of 55% and specificity of 90%. (11) ROC curve analysis of LncRNA-FA2H-2 in CHD patients showed AUC = 0.834 (0.688, 0.85) with a cut-off value of 3.155 and with a sensitivity of 85% and specificity of 82%. (12) Logistic analyses showed that TNF-α, MCP-1, VCAM-1, IL-6, and LncRNA-FA2H-2 were independent risk factors for CHD. The expression of LncRNA-FA2H-2 was reduced and inversely correlated with inflammation-related factors in CHD patients. LncRNA-FA2H-2 may have potential as an inflammatory marker for risk assessment of CHD development.

Acute myocarditis is a rare complication of urinary tract infection and sepsis. We report the case of a previously healthy 55-year-old female who presented to our emergency department with diarrhea and hypotension. The basic metabolic panel results showed an increase in inflammatory markers and an acute kidney injury. Urine and blood cultures grew . The patient subsequently developed sudden chest pain and shortness of breath, diffuse ST-segment elevation, and cardiac enzymes' elevation. Coronary angiogram was normal, and transthoracic echocardiogram demonstrated normal ventricular functions. Cardiac magnetic resonance imaging was highly suspicious of myopericarditis. The patient made a full recovery after infection treatment with intravenous antibiotics, aspirin, and colchicine.

We analyzed the inter- and intra-examiner reliability of Werium inertial sensors and the cervical range of motion (CROM) instrument for the measurement of active CROM (AcROM) in patients with primary headache. Another objective is to analyze the validity of the inertial sensors (Werium). The literature has reported symptomatology features in patients diagnosed with primary headache similar to that of patients with cervicogenic headache. The International Classification of Headache (ICHD-III) established the presence of reduced AcROM as a diagnostic criterion for cervicogenic headache. Several instruments are used for this measurement, with limitations in their applicability in daily clinical practice. A prospective longitudinal repeated measures study was conducted to assess the intra- and inter-rater reliability and validity of Werium inertial sensors in 20 adults with chronic primary headache. For the inter-rater analysis, the intraclass correlation coefficient (ICC) values were above 0.75 for all movements, indicating a good level of reliability. For the intra-rater results, the ICC values obtained by the Werium inertial sensors for all cervical movements were good for rater A (ICC >0.80) and rater B (ICC >0.84). For the validity, the ICCs obtained by the Werium inertial sensors compared with the CROM instrument for all cervical movements were moderate for both raters (ICC > 0.70, respectively). Values obtained in the standard error of measurement, minimum detectable change at 90% and limits of agreement also indicated good agreement. Werium inertial sensors have shown good to excellent reliability results, both intra- and inter-examiner (ICC > 0.75). Likewise, when the sensors were compared with another validated instrument (CROM device) they obtained high reliability results (ICC > 0.70). These results plus its relatively low price and ease of use allow us to recommend it in daily clinical practice to measure AcROM in patients with chronic primary headache.

Osteoarthritis (OA) is currently an incurable and progressive condition in dogs causing chronic joint pain and possibly increasing disability. Due to the poor healing capacity of cartilage lesions that occur with OA, development of effective therapeutics is difficult. For this reason, current OA therapy is mostly limited to the management of pain and inflammation, but not directed ad disease modification. In the search for a safe and effective OA treatment, mesenchymal stem cells (MSCs) have been of great interest since these cells might be able to restore cartilage defects. The designs of OA studies on MSC usage, however, are not always consistent and complete, which limits a clear evaluation of MSC efficacy. The general study results show a tendency to improve lameness, joint pain and range of motion in dogs suffering from naturally-occurring OA. Assessment of the cartilage surface demonstrated the ability of MSCs to promote cartilage-like tissue formation in artificially created cartilage defects. Immunomodulatory capacities of MSCs also seem to play an important role in reducing pain and inflammation in dogs. It should be mentioned, however, that in the current studies in literature there are specific design limitations and further research is warranted to confirm these findings.