There is a potential therapeutic application targeting brown adipose tissue (BAT). Either voluntary running or liraglutide increases the thermogenesis of BAT in type 2 diabetes mellitus, but their combined effect is not yet clarified. Male leptin receptor-deficient db/db diabetic mice (n = 24) were randomly divided into voluntary running, liraglutide, voluntary running + liraglutide, and control groups (n = 6/group). Normal male C57 mice were the negative control (n = 6). Fasting blood glucose was monitored every week, plasma insulin and lipid profiles were analyzed, and thermogenic protein expression in BAT and white adipose tissue (WAT) were analyzed by the western blot. A total of 128 metabolites associated with phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, and ceramides were targeted in BAT. Compared to the control group, voluntary running or liraglutide treatment significantly lowered the blood glucose and increased the insulin level; the combined group showed a better effect than liraglutide alone. Hence, the combined treatment showed an enhanced hypoglycemic effect. Uncoupling protein 1 (UCP1) and OXPHOS protein expression in BAT and UCP1 in WAT were significantly increased after exercise training and liraglutide treatment. However, BAT metabolomics showed that compared to the control mice, nine fatty acids increased in the exercise group, six increased in the liraglutide group, and only three increased in the combined group. These results may suggest a higher hypoglycemic effect and the activation of BAT and WAT browning in the combined group.

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Exudative pleural effusion includes tuberculous pleural effusion (TPE), parapneumonic pleural effusion (PPE), and malignant pleural effusion (MPE). An elevated pleural fluid adenosine deaminase (ADA) typically implies TPE, but the rule may not apply to every individual case. Recent studies proposed that the pleural fluid lactate dehydrogenase (LDH)-to-ADA ratio showed a higher diagnostic power than pleural fluid ADA alone in differentiating the etiology of pleural effusion. Hence, we aimed to investigate the performance of pleural fluid LDH-to-ADA ratio as a biomarker in assistance with the diagnosis of TPE, PPE, and MPE. All patients who underwent thoracentesis for the first time with a pleural fluid ADA >40 U/L were included in this retrospective study. The clinical data including pleural fluid ADA and LDH-to-ADA ratio were analyzed. A total of 311 patients were enrolled during the study interval. The pleural fluid LDH-to-ADA ratio <14.2 (sensitivity: 74.2%; specificity: 90.4%) favored TPE, while the pleural fluid LDH-to-ADA ratio >14.5 (sensitivity: 79.9%; specificity: 78.5%) favored PPE. Besides, the pleural fluid LDH-to-ADA ratio >46.7 (sensitivity: 56.3%; specificity: 78.3%) favored MPE owing to primary lung cancers. In conclusion, the pleural fluid LDH-to-ADA ratio was an effective indicator in differentiating the etiology of pleural effusions in the cases of high ADA level in the pleural fluid.

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Spasticity measured using clinical scales, such as the modified Ashworth scale (MAS), may not sufficiently evaluate the effectiveness of therapeutic interventions and predict prognosis. This study aimed to compare changes in H-reflex excitability in the spastic and unimpaired upper and lower limbs of patients with acute and chronic stroke. We also investigated the relationship between the degree of spasticity as assessed by the MAS and motor neuron pool excitability with by analyzing H-reflex excitability. Sixty adult patients with a first-ever stroke were recruited for this study. MAS scores were recorded in the post-stroke upper and lower limb muscles. H-reflexes and M-responses of the bilateral flexor carpi radialis and soleus were tested by stimulating the median and tibial nerves. The results showed that both the ratio of the maximal size of the H-reflex (Hmax) to the maximal size of the M-response (Mmax) and the ratio of the developmental slope of H-reflex (Hslp) to that of the M-responses (Mslp) were significantly higher on the spastic side than on the unimpaired side for the upper and lower limbs. In contrast, the ratio of the threshold of the H-reflex (Hth) to the threshold of the M-response (Mth) only showed significant differences between the two sides in the upper limbs. The Hslp/Mslp paretic/non-paretic ratio was increased in patients with MAS scores of 2 or 3 compared to MAS scores of 1 for both the upper and lower limbs, whereas the Hmax/Mmax paretic/non-paretic ratio showed significant differences between MAS scores of 2 or 3 and 1 only in the upper limbs. Moreover, in either the spastic or unimpaired sides, there were no significant differences in any of the three motoneuron pool excitability parameters, Hmax/Mmax, Hslp/Mslp, and Hth/Mth, between the shorter chronicity (time post-stroke ≤6 months) and longer chronicity groups (time post-stroke >6 months) for both the upper and lower limbs. These results suggest that Hslp/Mslp could be a potential neurophysiological indicator for evaluating the degree of spasticity in both the upper and lower limbs of patients with hemiplegia. The MAS and Hslp/Mslp characterize clinical and neurophysiologic spasticity, respectively, and could be used as an integrated approach to evaluate and follow up post-stroke spasticity.

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Cajanus cajan (L.) Millsp., known as pigeon pea, is one of the major grain legume crops of the tropical world. It recognizes as an ethnomedicine to possess various functions, such as helping in healing wound and cancer therapy. We investigated whether 95% ethanol extracts from C. cajan root (EECR) protect against methylglyoxal (MGO)-induced insulin resistance (IR) and hyperlipidemia in male Wistar rats and explored its possible mechanisms. The hypoglycemic potential of EECR was evaluated using α-amylase, α-glucosidase activities, and advanced glycation end products (AGEs) formation. For in vivo study, the rats were divided into six groups and orally supplemented with MGO except for Group 1 (controls). Group 2 was supplemented with MGO only, Group 3: MGO + metformin, Group 4: MGO + Low dose-EECR (L-EECR; 10 mg/kg bw), Group 5: MGO + Middle dose-EECR (M-EECR; 50 mg/kg bw), and Group 6: MGO + High dose-EECR (H-EECR; 100 mg/kg bw). EECR possessed good inhibition of α-glucosidase, α-amylase activities, and AGEs formation (IC₅₀ = 0.12, 0.32, and 0.50 mg/mL), respectively. MGO significantly increased serum levels of blood glucose (GLU), glycosylated hemoglobin, homeostasis model assessment of IR, AGEs, lipid biochemical values, and atherogenic index, whereas EECR decreased these levels in a dose-dependent manner. EECR can also act as an insulin sensitizer, which significantly decreased (47%, P < 0.05) the blood GLU levels after intraperitoneal injection of insulin in the insulin tolerance tests. The hypoglycemic and antihyperlipidemic mechanisms of EECR are likely through several possible pathways including the inhibition of carbohydrate-hydrolyzing enzymes (α-glucosidase and α-amylase) and the enhancement of MGO-trapping effects on inhibition of AGEs formation.

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This study aimed to assess (1) the reproducibility of three sperm chromatin dispersion (SCD) assays for sperm DNA fragmentation, i.e., LensHooke R10^® (R10), Halosperm G2^® (G2), and BASO^® (BA); (2) the correlation between computer-assisted semen analyzer (CASA) morphokinematic parameters and sperm DNA fragmentation index (DFI), and (3) the diagnostic value for male reproduction by combining semen morphokinematic parameters and DFI. Total 50 male participants were recruited, and all collected semen samples underwent semen analyses and SCD assays. Intra- and inter-observer variability of DFI data from different SCD measures was tested. In addition, the predictive ability of CASA parameters and DFI (with different cutoffs, i.e., 15% and 20%) for infertility was assessed using receiver operating characteristic curve analysis. We found that the G2 and R10 produced satisfactory variance coefficients (5.53%, 5.67%) compared to BA (14.8%). The DFI data from the R10 had lower intra-observer variability, in terms of higher intra-class coefficient (0.9615), than that of the G2 (0.8847) or BA (0.8824). Inter-observer variability of three SCD kits in scoring the DFI was comparable and satisfactory (concordance correlation coefficients ranging 0.9895–0.9630). The CASA parameters (i.e., total motility [r = −0.57], progression motility [r = −0.55], and rapidly progressive motility [r = −0.55]) were significantly correlated with DFI (P < 0.001). The predictive ability of the 15%-cutoff DFI data was better than that of the 20%-cutoff or continuous DFI data. The model comprising the CASA parameters, 15%-cutoff DFI, and 4%-cutoff normal morphology had the highest area under curve (0.8125) for infertility. For SCD assay, the R10 was the most reliable SCD assay to detect sperm DNA fragmentation. Combining the sperm DFI with CASA parameters might be a better diagnostic tool for male reproduction.

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Gomisin A is a dietary lignan compound isolated from the fruit of Schisandra chinensis and has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative activities. However, the benefit of gomisin A is still not well understood. The action of gomisin A is diverse. However, the effect of gomisin A on Ca²⁺ signaling in prostate cancer cells is unknown. Ca²⁺ is a pivotal second envoy that triggers and regulates cellular processes such as apoptosis, fertilization, energy transduction, secretion, and protein activation. The goal of this study was to explore the action of gomisin A on [Ca²⁺]_i and cytotoxicity in PC3 prostate cancer cells. Gomisin A at 100–200 μM provoked [Ca²⁺]_i raises. 20% of the response was reduced by removing external Ca²⁺. The Ca²⁺ influx provoked by gomisin A was suppressed by 20% by store-caused Ca²⁺ entry suppressors: econazole, SKF96365, nifedipine; also by phorbol 12-myristate 13 acetate and GF109203X. Without external Ca²⁺, gomisin A-caused [Ca²⁺]_i raises were abolished by thapsigargin. In contrast, gomisin A suppressed the [Ca²⁺]_i raises caused by thapsigargin. U73122 fell short to change gomisin A-caused [Ca²⁺]_i responses. Gomisin A (20–100 μM) elicited cytotoxicity in a dose-associated fashion. Blockade of [Ca²⁺] elevations with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid/acetoxy methyl failed to inhibit cytotoxicity of gomisin A. Collectively, gomisin A evoked [Ca²⁺]_i raises and provoked cytotoxicity in a Ca²⁺-dissociated fashion in prostate cancer cells.

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Coumarin has a variety of biological activities and widely exists in plants. Biscoumarin, derived from coumarin, their synthetic methods and bioactivities of biscoumarins is the hotspot of the current research. In this study, we evaluated for the first time the anticancer of a synthetic biscoumarin (3,3'-(4-chlorophenyl)methylene)bis(4-hydroxy-2H-chromen-2-one, C3) on lung cancer cells and explored the related mechanism. C3 was simply prepared by 4-hydroxycoumarin and 4-chlorobenzaldehyde under ethanol. The structure of C3 was elucidated by various spectroscopic analyses. The antiproliferation effect of C3 was evaluated by the cell counting kit-8 assay. Cell cycle and apoptosis analysis were detected by flow cytometry. The expression of correlated proteins was determined using Western blotting. The result showed that C3 displayed a strong cytostatic effect on Lewis lung cancer (LLC) cells. C3 inhibited the proliferation of LLC cells, and induced G2/M phase cell cycle arrest. In addition, C3 possessed a significant reduction on cell apoptosis by increasing of RIP1 expression. Our data showed that C3 suppresses lung cancer cell proliferation and induces cell apoptosis, which is possibly involved with the RIP1.

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