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To evaluate the short-term effects of Mulligan's mobilization with movement (MWM) on pain, physical function, emotional aspects, and proprioceptive acuity after a 2-week treatment period and throughout a 3-week follow-up period. A single group of 30 participants (60.96 ± 5.16 years) with symptomatic knee osteoarthritis (KOA) was evaluated. The protocol involved 5 evaluations moments, before (baseline) and after 2 weeks of intervention (24 hours after the last session), and at 3-week follow-up. The intervention included 3 Mulligan's MWM techniques. The variables evaluated were pain (pressure pain threshold and Visual Numeric Scale), physical function (range of motion, proprioceptive acuity, and the Western Ontario and McMaster Universities Osteoarthritis Index) and emotional aspects (Beck Depression Inventory). Analysis of variance for repeated measures was used considering a significance level of 5%. At the second evaluation (after intervention), the pressure pain threshold presented higher values for rectus femoris, tibialis anterior, and patellar tendon sites and reduced values for the Visual Numeric Scale, Beck Depression Inventory, and Western Ontario and McMaster Universities Osteoarthritis Index compared with baseline. Also, during the follow-up period, all variables returned close to baseline levels. Proprioceptive acuity and range of motion did not present significant changes. Scores for pain relief, physical function, and emotional aspects improved after a course of MWM in this single group of individuals with KOA. Mobilization with movement had limited outcome during follow-up. It suggests that future clinical trials on the use of MWM for KOA should be considered. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: To describe the ultrasound characteristics of gouty tophi in the olecranon bursa and to evaluate their reproducibility. Methods: A prospective study of the ultrasound features of 35 sites of tophi nodulations in the elbows of 31 men (mean 54.6 years). The findings were evaluated dynamically following pre-established standards. The static images were evaluated by another radiologist and were reviewed by the first examiner. Results: The most frequent characteristics of tophi are: hyperechogenicity (91.7%), poorly defined contours (88.6%), multiple grouped nodules (85.6%) and heterogeneity (68.6%). Intra-observer agreement is almost perfect for echogenicity (K =1.0), moderate for the involvement of the olecranon bursa (K =0.47) and fair for other characteristics. Inter-observer agreement is substantial for the echogenicity (K =0.65), fair for the echotexture (K =0.27) and the presence of a perilesional hypoechoic halo (K =0.34) and slight for other characteristics. Conclusions: The most frequent characteristic of tophi is hyperechogenicity. The intra-observer and inter-observer concordance for echogenicity are almost perfect and substantial, respectively. Knowledge of characteristics of the tophi in the elbow and their intra and inter-observer reproducibility may assist in establishing parameters for monitoring treatment and setting up criteria for differential diagnosis of processes involving the olecraneon bursa. [Copyright &y& Elsevier]

Immune-mediated cerebellar ataxias were initially described as a clinical entity in the 1980s, and since then, an expanding body of evidence has contributed to our understanding of this topic. These ataxias encompass various etiologies, including postinfectious cerebellar ataxia, gluten ataxia, paraneoplastic cerebellar degeneration, opsoclonus-myoclonus-ataxia syndrome and primary autoimmune cerebellar ataxia. The increased permeability of the brain-blood barrier could potentially explain the vulnerability of the cerebellum to autoimmune processes. In this manuscript, our objective is to provide a comprehensive review of the most prevalent diseases within this group, emphasizing clinical indicators, pathogenesis, and current treatment approaches. • Immune-mediated processes can give rise to disabling cerebellar ataxia. • The immune-mediated cerebellar ataxias are potentially treatable. • The early treatment in autoimmune cerebellar conditions is imperative. • Acute cerebellar ataxia with vermian involvement should raise suspicion. [ABSTRACT FROM AUTHOR]

Hydrocotyle umbellata L. is a medicinal herb for the treatment of some health problems including hypertension, according to traditional medicine. Even so, its vascular effects and the pharmacological action mechanisms have not been analyzed. This experiment aimed to analyze the effects of hydroalcoholic extract of Hydrocotyle umbellata L. (HEHU) on isolated vessels and verify the interaction of hibalactone (chemical marker) against Ca v 1.2 channels using molecular docking. Vascular reactivity experiments were performed using rat aortas with (E+) or without endothelium (E−) in an isolated organ bath. Computational molecular docking approaches were used to show the direct effect on L-type Ca2+ Channels. HEHU (0–560 μg/mL) induced relaxation of the pre-contracted arteries in a concentration-dependent manner. The maximum effect was higher in E+ (76.8 ± 4.1%) as compared to E− (47.3 ± 5.5%). Pre-treatment of E+ arteries with L-NAME or ODQ reduced the relaxation to similar level of E− arteries. The treatment of arteries with MDL-12,330 A, diclofenac, propranolol and atropine did not change the relaxation induced by HEHU. The contraction caused by internal Ca2+ release induced by caffeine was reduced after HEHU treatment. Moreover, the HEHU also impaired the contraction induced by Ca2+ influx stimulated with phenylephrine or high KCl. The docking study demonstrated the effectiveness of hibalactone in blocking the Ca v 1.2 channel. These findings show that HEHU induces vascular relaxation which is potentiated (but not dependent) by endothelial cells. Blocking of Ca2+ influx seems to be the main mechanism for the vascular effects of HEHU. [Display omitted] [ABSTRACT FROM AUTHOR]

Fatty acid accumulation in hepatocytes induced by high concentrations of fatty acids due to lipolysis and the associated oxidative damage they cause occur most frequently after calving. Because of their role in esterification of fatty acids, diacylglycerol acyltransferase isoforms (DGAT1 and DGAT2) could play a role in the susceptibility of dairy cows to develop fatty liver. To gain mechanistic insights, we performed in vivo and in vitro analyses using liver biopsies or isolated primary hepatocytes. The in vivo study (n = 5 cows/group) involved healthy cows [average liver triacylglycerol (TAG) = 0.78%; 0.58 to 0.93%, ratio of triglyceride weight to wet liver weight] or cows diagnosed with fatty liver (average TAG = 7.60%; 5.31 to 10.54%). In vitro, hepatocytes isolated from 3 healthy female calves (1 d old, 44 to 53 kg) were challenged with (fatty acids) or without (control) a 1.2 m M mixture of fatty acids in an attempt to induce metabolic stress. Furthermore, hepatocytes were treated with DGAT1 inhibitor or DGAT2 inhibitor for 2 h followed by a challenge with (DGAT1 inhibitor + fatty acids or DGAT2 inhibitor + fatty acids) or without (DGAT1 inhibitor or DGAT2 inhibitor) the 1.2 m M mixture of fatty acids for 12 h. Data analysis of liver biopsies was compared using a 2-tailed unpaired Student's t -test. Data from calf hepatocyte treatment comparisons were assessed by one-way ANOVA, and multiplicity for each experiment was adjusted by the Holm's procedure. Data indicated that both fatty liver and in vitro challenge with fatty acids were associated with greater mRNA and protein abundance of SREBF1, FASN, DGAT1, and DGAT2. In contrast, mRNA and protein abundance of CPT1A and very low-density lipoprotein synthesis-related proteins MTTP and APOB were markedly lower. However, compared with fatty acid challenge alone, DGAT1 inhibitor + fatty acids led to greater mRNA and protein abundance of CPT1A and APOB, and greater mRNA abundance of SREBF1 and MTTP. Furthermore, this treatment led to lower mRNA abundance of FASN and DGAT2 and TAG concentrations. Compared with fatty acid challenge alone, DGAT2 inhibitor + fatty acids led to greater mRNA and protein abundance of CPT1A, MTTP, and APOB, and lower mRNA and protein abundance of SREBF1 and FASN. In addition, compared with control and fatty acids, there was greater protein abundance of GRP78 and PERK in both DGAT1 and DGAT2 inhibitor with or without fatty acids. Furthermore, compared with control and fatty acids, reactive oxygen species concentrations in the DGAT1 inhibitor with or without fatty acid group was greater. Overall, data suggested that DGAT1 is particularly relevant in the context of hepatocyte TAG synthesis from exogenous fatty acids. Disruption of both DGAT1 and DGAT2 altered lipid homeostasis, channeling fatty acids toward oxidation and generation of reactive oxygen species. Both DGAT isoforms play a role in promoting fatty acid storage into TAG and lipid droplets to protect hepatocytes from oxidative damage. [ABSTRACT FROM AUTHOR]

• An Eco-friendly packaging based on cassava starch, gelatin and casein was developed. • Medium values of opacity and low water vapor transmission rate were observed. • The biodegradable film increased the guavas shelf-life by 2 days. Coating fruits surface with biodegradable films obtained from starch is an alternative to delay the fruit ripening process. This study aimed to develop a biodegradable film from a polymer blend consisting of natural cassava starch, casein, and gelatin, and using sorbitol as the plasticizer. Among all the prepared biodegradable films (BFs), the one with desirable results in thickness, opacity, solubility, and water vapor transmission rate (WVTR) analyzes was based on a high concentration of starch, and casein, and low concentration of gelatin. Also, this film had the lowest solubility among all of them. Guava fruit coated with this film showed a two-day increase in shelf-life when compared to non-coated guavas. The increase in shelf-life was due to the extremely low water vapor transmission rate of the films, decreasing the fruits' mass loss, and, consequently, retarding their senescence. These results indicate that the biodegradable film is a promising material for fruit coating. [ABSTRACT FROM AUTHOR]

[Display omitted] • New twenty-three hybrids bisnaphthoquinone x 1,2,3-1 H -triazole were developed. • All compounds were screened against breast cancer cell lines MCF-7 and MDA-MB-231. • Some compounds presented as potential new drugs for cancer treatment. • Two of them (12g and 12h) two of them were selective with low toxicity. • 12g and 12h are novel AMPK activators presenting selective antitumor effects. The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1 H -triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects. [ABSTRACT FROM AUTHOR]

Abstract: MjTX-II, a myotoxic phospholipase A2 (PLA2) homologue from Bothrops moojeni venom, was functionally and structurally characterized. The MjTX-II characterization included: (i) functional characterization (antitumoral, antimicrobial and antiparasitic effects); (ii) effects of structural modifications by 4-bromophenacyl bromide (BPB), cyanogen bromide (CNBr), acetic anhydride and 2-nitrobenzenesulphonyl fluoride (NBSF); (iii) enzymatic characterization: inhibition by low molecular weight heparin and EDTA; and (iv) molecular characterization: cDNA sequence and molecular structure prediction. The results demonstrated that MjTX-II displayed antimicrobial activity by growth inhibition against Escherichia coli and Candida albicans, antitumoral activity against Erlich ascitic tumor (EAT), human breast adenocarcinoma (SK-BR-3) and human T leukemia cells (JURKAT) and antiparasitic effects against Schistosoma mansoni and Leishmania spp., which makes MjTX-II a promising molecular model for future therapeutic applications, as well as other multifunctional homologous Lys49-PLA2s or even derived peptides. This work provides useful insights into the structural determinants of the action of Lys49-PLA2 homologues and, together with additional strategies, supports the concept of the presence of others “bioactive sites” distinct from the catalytic site in snake venom myotoxic PLA2s. [Copyright &y& Elsevier]

Tuberculosis (TB) is one of the most fatal diseases and is responsible for the infection of millions of people around the world. Most recently, scientific frontiers have been engaged to develop new drugs that can overcome drug-resistant TB. Following this direction, using a designed scaffold based on the combination of two separate pharmacophoric groups, a series of menadione-derived selenoesters was developed with good yields. All products were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv and attractive results were observed, especially for the compounds 8a , 8c and 8f (MICs 2.1, 8.0 and 8.1 μM, respectively). In addition, 8a , 8c and 8f demonstrated potent in vitro activity against multidrug-resistant clinical isolates (CDCT-16 and CDCT-27) with promising MIC values ranging from 0.8 to 3.1 μM. Importantly, compounds 8a and 8c were found to be non-toxic against the Vero cell line. The SI value of 8a (>23.8) was found to be comparable to that of isoniazid (>22.7), which suggests the possibility of carrying out advanced studies on this derivative. Therefore, these menadione-derived selenoesters obtained as hybrid compounds represent promising new anti-tubercular agents to overcome TB multidrug resistance. Image 1 • New menadione-derived selenoesters were synthesized. • The compounds demonstrated excellent activity against M. tuberculosis H37Rv. • 8a , 8c and 8f showed potent activity against multidrug resistant clinical isolates. • Compounds 8a and 8c were found to be non-toxic. • These organoselenium compounds represent promising new anti-tubercular agents. [ABSTRACT FROM AUTHOR]