Significant Increase In Activity Research Articles

Preventing Type 2 Diabetes after Gestational Diabetes: A Systematic Review Mapping Physical Activity Components using the Socio-Ecological Model.

Gestational diabetes commonly occurs during pregnancy and increases lifetime risk of type 2 diabetes following pregnancy. Engaging in physical activity postnatally can reduce this subsequent risk. Interventions aiming to increase physical activity after gestational diabetes may not address the wide range of post-pregnancy barriers. A socio-ecological approach highlights the need to include multi-level factors such as social, community and organisational factors. The aim of the review was to map intervention components to prevent type 2 diabetes after gestational diabetes using the socio-ecological model as a framework and investigate how physical activity changes align with different intervention components utilised. Eligible studies included any study type within 5 years of a gestational diabetes diagnosis and targeted physical activity. A systematic search of MEDLINE, Cochrane Library, Web of Science, CINAHL Complete, and Scopus was conducted in October 2022. Results were categorised based on whether findings demonstrated no increases, non-statistically significant increases or statistically significant increases in physical activity. Forty-eight studies were included (37 different interventions). Thirty-eight studies were assessed as "adequate" quality, only two studies were "good" quality, and the remaining were limited quality. Mixed physical activity outcomes were observed across components used at the intrapersonal level, with components across other levels of the socio-ecological model showing more increases in physical activity. Intervention components within the social and organisational levels, for example childcare provision, providing group-based sessions and offering remote delivery, were more often present in interventions with physical activity increases. Future interventions targeting physical activity after gestational diabetes should aim to include social and organisational-level components in their intervention design. This systematic review was registered in PROSPERO (ID: CRD42021272044).

Lambda-Cyhalothrin induced behavioural, neurotoxic and oxidative stress on vertebrate model Danio rerio (Hamilton-Buchanan 1822).

λ-cyhalothrin, a synthetic type II pyrethroid, has become increasingly popular for control of aphids, butterfly larvae, and beetles, replacing other agricultural chemicals. As a result of which, residues of this synthetic pesticide are being reported across the globe in natural water, which poses a serious threat to aquatic life. Therefore, the present study was designed to understand the toxicity effects of λ-cyhalothrin on behaviour, oxidative stress and neurotoxicity in a vertebrate aquatic model, zebrafish (Danio rerio). The fish were exposed to 0.129, 0.194 and 0.388 µg/L corresponding to 5%, 10% and 20% of 96hLC50 (1.94 µg/L) for 28 days. Upon exposure to the highest concentration (0.388 µg/L), the test animal exhibited significant alterations in behavioural patterns like number of entries to the top zone (n), decrease in average speed (m/s) and decrease in time spent in top zone (s). Moreover, the shoaling test demonstrated a significant decrease (p < 0.05) in the relative time spent by the tested fish (%) near the stimulus fish. The change in behavioural alterations might be linked to a significant decrease (p < 0.05) in the brain acetylcholine esterase activity. Furthermore, the present study also illustrates oxidative stress exerted by λ-cyhalothrin through an increase in the production of reactive oxygen species, which is again clearly depicted by a significant increase (p < 0.05) in Superoxide dismutase, Catalase and Glutathione peroxidase activities. Overall, the present study systematically demonstrates the chronic effects of λ-cyhalothrin on adult fish behaviour and physiology, which will contribute to assessing the risks of λ-cyhalothrin to organismal health.

Natural antibodies targeting LPS in pleural effusions of various etiologies.

Respiratory infection, cancer, and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal-associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum (S) having a major role in systemic and mucosal immunity; however, their occurrence in pleural fluid (PF) remains an open question. Our aim herein was to detect and measure the levels of NAbs (IgM, IgG, IgA) targeting lipopolysaccharides (LPS) in both the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG, and IgA levels, all determined by in-house ELISA. In addition, the ratios of PF/S values were analyzed further with other critical biochemical parameters from pleural fluids. Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and noninfectious compared with malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. Our results highlight the role of anti-LPS NAbs in the pleural cavity and demonstrate the potential translational impact that should be further explored.NEW & NOTEWORTHY Here we describe the detection and quantification of natural antibodies (NAbs) in the human pleural cavity. We show for the first time that IgM, IgG, and IgA anti-LPS natural antibodies are detected and measured in pleural effusions of infectious, noninfectious, and malignant etiologies and provide clinical correlates to demonstrate the translational impact of our findings.

A crucial role of adenosine deaminase in regulating gluconeogenesis in mice

Adenosine deaminase (ADA) catalyzes the irreversible deamination of adenosine to inosine and regulates adenosine concentration. ADA ubiquitously expresses in various tissues to mediate adenosine receptor signaling. A significant increase in plasma ADA activity has been shown to be associated with the pathogenesis of type 2 diabetes mellitus (T2DM). Here we show that elevated plasma ADA activity is a compensated response to high level of adenosine in T2DM and plays an essential role in the regulation of glucose homeostasis. Supplementing with more ADA, instead of inhibiting ADA can reduces adenosine levels and decreases hepatic gluconeogenesis. ADA restores a euglycemic state and recovers functional islets in db/db and high-fat-STZ diabetic mice. Mechanistically, ADA catabolizes adenosine and increases Akt and FoxO1 phosphorylation independent of insulin action. ADA lowers blood glucose at a slower rate and longer duration compared to insulin, delaying or blocking the incidence of insulinogenic hypoglycemia shock. Finally, ADA suppresses gluconeogenesis in fasted mice and insulin-deficient diabetic mice, indicating the ADA regulating gluconeogenesis is a universal biological mechanism. Overall, these results suggest that ADA is expected to be a new therapeutic target for diabetes.

Alnus glutinosa (Alder) sapling as a phytoremediator for cadmium in contaminated soil of industrial park

Heavy metals can contaminate soil through human activities such as mining, waste disposal, excessive use of chemical fertilizers, and fossil fuels. In Iran, uncontrolled urban growth and lack of waste collection systems have led agricultural lands to become receptors of urban and industrial waste, resulting in the contamination of soil with cadmium, which has negative consequences for the environment and health. Alder sapling may have considerable potential for phytoremediation. The soil was placed in plastic pots of 40 cm in diameter with 7 kg air-dried weight soil per pot, spiked with solutions of cadmium chloride [Cd Cl2.H2O] at rates of 0 (control), 50, 100, 150, and 200 mg/kg in a solution. The analyzed data revealed a significant reduction in vegetative growth (plant height, leaf area, chlorophyll, stem diameter growth, stem dry weight, root dry weight, and leaves dry weight). The means were compared to assess the impact of cadmium accumulation on certain biochemical and physiological characteristics. The mean separation was performed using Duncan's Multiple Range test with a p-value ≤0.05. However, there was a simultaneous significant increase in enzymatic activities (peroxidase and catalase) and an increase in proline compared to control plants. The bioconcentration factor of stem, leaves, and roots was under one. The translocation factor (TF) of cadmium was more than 1, and cadmium contents were more localized in roots compared to leaves and stems, minimizing the risk of contamination through leaves. Alnus glutinosa has defense mechanisms against cadmium up to 19.5 mg/kg soil, as the tolerance index for roots and biomass is more than 0.8. Finally, it is a good candidate for research on phytoremediation and phytoextraction.

Do political affiliation and economic wellbeing thwart religious identification in China?

Abstract While the Chinese government's stated position is to support religious freedom, the Chinese Communist Party (CCP) is officially atheist. Individuals who profess faith are typically unable to join and members who practice a religion face expulsion and a loss of benefits. This paper analyzes the extent to which the CCP's policies regarding religion may influence religious identification over the life cycle in China. To do so, we contrast changes in religious affiliation before and after retirement for CCP members and non-CCP members. We find a significant increase of religious activities and religious faith in CCP members after retirement – suggesting: (1) people's acknowledgment of religious belief is significantly influenced by CCP regulations and (2) the biggest influence from a material benefits perspective occurs for those CCP members employed in the Chinese government system.

Outcomes for breast cancer survivors with metastatic disease in a physical activity program for medically underserved cancer survivors.

This study examined the effectiveness and feasibility of the Active Living After Cancer (ALAC) program for metastatic breast cancer (MBC) survivors. ALAC is a 12-session community-based program to help cancer survivors improve their physical functioning and quality of life through increased physical activity. ALAC participants with MBC (stage IV) were compared to survivors with early-stage breast cancer (stages I and II). The International Physical Activity Questionnaire, Godin Leisure-Time Physical Activity, 30-second sit-to-stand test, and PROMIS Global Health were administered at baseline and follow-up. Program satisfaction and retention were assessed at week 12. Repeated-measures mixed models were used to compare changes in outcomes between survivors with early-stage breast cancer and MBC. A total of 585 women (59.3 y ± 10.6), most of whom were Hispanic (54%) or non-Hispanic Black (22%), were included (early stage, n = 538; MBC, n = 47). After the ALAC program, a significant increase in physical activity (P < 0.001), improved physical and mental health T-scores (P < 0.001), and more sit-to-stand repetitions (P < 0.001) were observed for both survivors with early-stage breast cancer and MBC. Women with MBC showed significantly lower physical health (P = 0.037) and physical function (P = 0.010) compared to early-stage at baseline. The ALAC program increased physical activity and improved health-related quality of life and physical function among breast cancer survivors with both early-stage and metastatic disease. This study emphasizes the importance of incorporating physical activity interventions like the ALAC program into the comprehensive care of cancer survivors, including those with metastatic disease.

Antimicrobial topical polymeric films loaded with Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid and silver nanoparticles: Optimization, characterization, and biological activity

The study examined the antimicrobial and antioxidant potential of pure Acetyl-11-keto-β-boswellic acid (AKBA), boswellic acid (70%) and AKBA loaded nanoparticles as topical polymeric films. The optimized concentration (0.05 % w/v) of pure AKBA, boswellic acid (BA), and AKBA loaded silver nanoparticles were used to study its impact on film characteristics. Carboxymethyl cellulose (CMC), sodium alginate (SA), and gelatin (Ge) composite films were prepared in this study. The polymeric films were evaluated for their biological (antioxidant and antimicrobial activities) and mechanical characteristics such as tensile strength (TS) and elongation (%). Moreover, other parameters including water barrier properties and color attributes of the film were also evaluated. Furthermore, assessments were conducted using analytical techniques like FTIR, XRD, and SEM. Surface analysis revealed that AgNP precipitation led to a few particles in the film structure. Overall, the results indicate a relatively consistent microstructure. Moreover, due to the addition of AKBA, BA, and AgNPs, a significant decrease in TS, moisture content, water solubility, and water vapor permeation was observed. The films transparency also showed a decreasing trend, and the color analysis revealed decreasing yellowness (b*) of the films. Importantly, a significant increase in antioxidant activity against DPPH free radicals and ABTS cations was observed in the CSG films. Additionally, the AgNP-AKBA loaded films displayed significant antifungal activity against C. albicans. Moreover, the molecular docking analysis revealed the inter-molecular interactions between the AKBA, AgNPs, and composite films. The docking results indicate good binding of AKBA and silver nanoparticles with gelatin and carboxymethyl cellulosemolecules. In conclusion, these polymeric films have potential as novel materials with significant antioxidant and antifungal activities.

The effect of silver nanoparticles and preparations of various pharmacological groups on the bactericidal activity of &lt;i&gt;Staphylococcus aureus&lt;/i&gt;

Multidrug-resistant bacteria have become one of the most serious threats to public health worldwide. The abuse of antibiotics has contributed to the emergence and transmission of resistance mechanisms among bacteria, jeopardizing the therapeutic potential of antibiotics. Uncontrolled use of drugs leads to the formation of antibiotic resistance due to mutations in chromosomal DNA, as well as the production of plasmids, integrons from other bacteria during horizontal gene transfer. In 2010, the BRICS countries (Brazil, Russia, India, China and South Africa) accounted for 76% of antibiotic consumption, with India consuming 12.9 billion units and China – 10 billion units. As of 2017, carbapenem-resistant Acetobacter baumannii and Enterobacteriaceae resulted in approximately US$ 281 million in healthcare costs in the United States. According to numerous reports from the Center for Disease Control and Prevention, approximately 2.3 million episodes of multidrug-resistant microbial diseases resulting in 25,000 deaths are recorded annually in the United States alone. In this regard, the world community of scientists has intensified the study of the combined use of various antibacterial drugs to achieve maximum bactericidal activity. Studies have been conducted to determine the synergistic effect when using combinations of drugs of various pharmacological groups and silver nanoparticles. A significant increase in bactericidal activity by 53.87 times (from 2.528 to 0.0098 mcg/ml) was found with the combined use of AgNPs and DSMO against the reference strain Staphylococcus aureus ATCC 25953. While the cultivation of St. aureus isolate with DSMO and silver nanoparticles revealed a sensitivity increase of 128.2 times (from 5.056 to 0.039 mcg/ml).

Acute Autonomic Nervous System Response to Direct Sacral Nerve Root Stimulation in Lower Urinary Tract Dysfunction: A New Approach to Understand the Mechanism of Action of Sacral Nerve Modulation.

Our goal was to assess acute autonomic nervous system (ANS) response to direct sacral nerve root (SNR) stimulation in the context of lower urinary tract dysfunction. In this retrospective monocentric study, patients undergoing 2-stage sacral nerve modulation for overactive bladder, nonobstructive urinary retention, or chronic bladder pain syndrome between March 2022 and June 2023 were analyzed. A standardized stimulation protocol was applied during the lead implantation, each of the 4 contact points being sequentially stimulated at the amplitude required to elicit anal motor response. Stimulations were labeled as StimA, StimB, StimC, and StimD, ordered by ascending order of minimum amplitude required for anal motor response. Heart rate variability parameters were collected using PhysioDoloris Monitor, and computed through the time-domain (standard deviation of normal-to-normal intervals [SDNN], root mean square of successive differences), the frequency-domain (low frequency, high frequency) and the graphical (Analgesia Nociception Index [ANI]) methods. Fifty patients were analyzed, including 35 females. Twelve patients had an underlying neurological disease. Efficacy was deemed achieved in 54% of patients. SDNN variability significantly increased during StimA to StimC, while maximum SDNN significantly increased only during StimA. ANI variability significantly increased during all 4 stimulations, while maximum ANI significantly increased only during StimA. Direct stimulation of SNR is responsible for a significant increase in ANS and relative parasympathetic nervous system activity, with a greater effect observed when the stimulation was delivered closer to the SNR. These results shed light on potential mechanisms underlying sacral nerve modulation, particularly regarding the treatment of ANS dysregulation in lower urinary tract dysfunction.

A C-type lectin with dual carbohydrate recognition domains functions in innate immune response in Asian corn borer, Ostrinia furnacalis.

C-type lectins (CTLs) act as pattern recognition receptors (PRRs) to initiate the innate immune response in insects. A CTL with dual carbohydrate recognition domains (CRDs) (named immulectin-4 [IML-4]) was selected from the Ostrinia furnacalis transcriptome dataset for functional studies. We cloned the full-length complementary DNA of O. furnacalis IML-4 (OfIML-4). It encodes a 328-residue protein with a Glu-Pro-Asn (EPN) and Gln-Pro-Asp (QPD) motifs in 2 CRDs, respectively. OfIML-4 messenger RNA levels increased significantly upon the bacterial and fungal infection. Recombinant OfIML-4 (rIML-4) and its individual CRDs (rCRD1 and rCRD2) exhibited the binding ability to various microorganisms including Escherichia coli, Micrococcus luteus, Pichia pastoris, and Beauveria bassiana, and the cell wall components including lipopolysaccharide from E. coli, peptidoglycan from M. luteus or Bacillus subtilis, and curdlan from Alcaligenes faecalis. The binding further induced the agglutination of E. coli, M. luteus, and B. bassiana in the presence of calcium, the phagocytosis of Staphylococcus aureus by the hemocytes, in vitro encapsulation and melanization of nickel-nitrilotriacetic acid beads, and a significant increase in phenoloxidase activity of plasma. In addition, rIML-4 significantly enhanced the phagocytosis, nodulation, and resistance of O. furnacalis to B. bassiana. Taken together, our results suggest that OfIML-4 potentially works as a PRR to recognize the invading microorganisms, and functions in the innate immune response in O. furnacalis.

New insights into the milk quality at varying altitudes in China

Introducing Holstein cows on Qinghai-Tibetan Plateau is a potential solution to enhance local milk production. However, the relationship between milk quality and altitude in China remains unknown. Therefore, the components and plasmin (PL) system of raw milk from different altitudes (sea level, 1600, 2700, and 3800 m) were investigated. The daily milk production of Holstein cows and PL activity decreased as the altitude increased. However, the components content of raw milk, plasminogen (PLG)/PL ratio, activities of PLG and plasmin activator (PA) increased with altitude. The pasteurization resulted a significant decrease in PA activity of all milk and a significant increase in PL activity in milk collected at higher altitudes (2700 and 3800 m), suggesting the pasteurization was unsuitable for preserving milk at higher altitudes. This study offered references for the production and storage of milk after introducing Holstein cows on Qinghai-Tibetan Plateau.

WSSV early protein WSSV004 enhances viral replication by suppressing LDH activity

White spot syndrome virus (WSSV) is known to upregulate glycolysis to supply biomolecules and energy for the virus's replication. At the viral genome replication stage, lactate dehydrogenase (LDH), a glycolytic enzyme, shows increased activity without any increase in expression. In the present study, yeast 2-hybrid screening was used to identify WSSV proteins that interacted with LvLDH isoform 1 and 2, and these included the WSSV early protein WSSV004. The interaction between WSSV004 and LvLDH1/2 was confirmed by co-immunoprecipitation. Immunofluorescence showed that WSSV004 co-localized with LvLDH1/2 in the cytoplasm. dsRNA silencing experiments showed that WSSV004 was crucial for WSSV replication. However, although WSSV004 silencing led to the suppression of total LvLDH gene expression during the viral late stage, there was nevertheless a significant increase in LvLDH activity at this time. We also used affinity purification-mass spectrometry to identify cellular proteins that interact with WSSV004, and found a total of 108 host proteins and 3 WSSV proteins with which it potentially interacts. Bioinformatics analysis revealed that WSSV004 and its interacting proteins might be responsible for various biological pathways during infection, including vesicular transport machinery and RNA-related functions. Collectively, our study suggests that WSSV004 serves as a multifunctional modulator to facilitate WSSV replication.

Apoplastomes of contrasting cacao genotypes to witches' broom disease reveals differential accumulation of PR proteins.

Witches' broom disease (WBD) affects cocoa trees (Theobroma cacao L.) and is caused by the fungus Moniliophthora perniciosa that grows in the apoplast in its biotrophic phase and later progresses into the tissues, causing serious losses in the production of cocoa beans. Therefore, the apoplast of T. cacao can provide important defense responses during the interaction with M. perniciosa. In this work, the protein profile of the apoplast of the T. cacao genotypes Catongo, susceptible to WBD, and CCN-51, resistant one, was evaluated. The leaves of T. cacao were collected from asymptomatic plants grown in a greenhouse (GH) and from green witches' brooms grown under field (FD) conditions for extraction of apoplastic washing fluid (AWF). AWF was used in proteomic and enzymatic analysis. A total of 14 proteins were identified in Catongo GH and six in Catongo FD, with two proteins being common, one up-accumulated, and one down-accumulated. In CCN-51, 19 proteins were identified in the GH condition and 13 in FD, with seven proteins being common, one up-accumulated, and six down-accumulated. Most proteins are related to defense and stress in both genotypes, with emphasis on pathogenesis-related proteins (PR): PR-2 (β-1,3-glucanases), PR-3 and PR-4 (chitinases), PR-5 (thaumatine), PR-9 (peroxidases), and PR-14 (lipid transfer proteins). Furthermore, proteins from microorganisms were detected in the AWF. The enzymatic activities of PR-3 showed a significant increase (p < 0.05) in Catongo GH and PR-2 activity (p < 0.01) in CCN-51 FD. The protein profile of the T. cacao apoplastome offers insight into the defense dynamics that occur in the interaction with the fungus M. perniciosa and offers new insights in exploring future WBD control strategies.

The Effect of Tuna Extract on Periarticular Tissue Catalase Activity and Malondialdehyde Levels in Animal Models of Adjuvant Arthritis

Tuna contains vitamins, minerals, amino acids, and fatty acids, which play a role in preventing oxidative stress. The pathophysiology of rheumatoid arthritis is often associated with oxidative stress due to increased ROS production. Adjuvant arthritis experimental animals are widely used for research on rheumatoid arthritis. This study aims to determine the effect of tuna fish extract on plasma malondialdehyde (MDA) levels and periarticular tissue catalase in adjuvant arthritis (AA) experimental animals with AA. The 24 experimental animals were divided into 3 groups, group 1, eight experimental animals without treatment; group 2, eight experimental animals AA-induced complete freund adjuvant (CFA); group 3, eight experimental animals AA treated with Tuna fish extract therapy, and at the end of the study the animals were sacrificed and examined for plasma MDA and periarticular tissue catalase levels. The results of the ANOVA statistical test showed a significant increase in periarticular tissue catalase activity (p=0.001) between the AA group and the treatment group. There was a considerable decrease in periarticular tissue MDA levels (p=0.001) between the adjuvant arthritis group and the treatment group with p value = 0.001. The Spearman correlation test between MDA levels and catalase activity shows -0.335, indicating an adequate and inverse correlation. The administration of tuna extract can prevent oxidative stress. It can be shown that increasing the antioxidant activity of catalase and reducing lipid peroxidation is measured by examining MDA levels.

A randomized, double-blind, placebo-controlled study on immune improvement effects of ethanolic extract of Echinacea purpurea (L.) Moench in Korean adults.

Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults.

Adipocyte-specific disruption of the BBSome causes metabolic and autonomic dysfunction.

Obesity is a major public health issue due to its association with type 2 diabetes, hypertension, and other cardiovascular risks. The BBSome, a complex of eight conserved Bardet-Biedl syndrome (BBS) proteins, has emerged as a key regulator of energy and glucose homeostasis as well as cardiovascular function. However, the importance of adipocyte BBSome in controlling these physiological processes is not clear. Here, we show that adipocyte-specific constitutive disruption of the BBSome through selective deletion of the Bbs1 gene adiponectin (AdipoCre/Bbs1fl/fl mice) does not affect body weight under normal chow or high-fat and high-sucrose diet (HFHSD). However, constitutive BBSome deficiency caused impairment in glucose tolerance and insulin sensitivity. Similar phenotypes were observed after inducible adipocyte-specific disruption of the BBSome (AdipoCreERT2/Bbs1fl/fl mice). Interestingly, a significant increase in renal sympathetic nerve activity, measured using multifiber recording in the conscious state, was observed in AdipoCre/Bbs1fl/fl mice on both chow and HFHSD. A significant increase in tail-cuff arterial pressure was also observed in chow-fed AdipoCre/Bbs1fl/fl mice, but this was not reproduced when arterial pressure was measured by radiotelemetry. Moreover, AdipoCre/Bbs1fl/fl mice had no significant alterations in vascular reactivity. On the other hand, AdipoCre/Bbs1fl/fl mice displayed impaired baroreceptor reflex sensitivity when fed HFHSD, but not on normal chow. Taken together, these data highlight the relevance of the adipocyte BBSome for the regulation of glucose homeostasis and sympathetic traffic. The BBSome also contributes to baroreflex sensitivity under HFHSD, but not normal chow.NEW & NOTEWORTHY The current study show how genetic manipulation of fat cells impacts various functions of the body including sensitivity to the hormone insulin.

Mode of action analysis for fluxapyroxad-induced rat liver tumour formation: evidence for activation of the constitutive androstane receptor and assessment of human relevance

The fungicide fluxapyroxad (BAS 700 F) has been shown to significantly increase the incidence of liver tumours in male Wistar rats at dietary levels of 1500 and 3000 ppm and in female rats at a dietary level of 3000 ppm via a non-genotoxic mechanism. In order to elucidate the mode of action (MOA) for fluxapyroxad-induced rat liver tumour formation a series of in vivo and in vitro investigative studies were undertaken. The treatment of male and female Wistar rats with diets containing 0 (control), 50, 250, 1500 and 3000 ppm fluxapyroxad for 1, 3, 7 and 14 days resulted in a dose-dependent increases in relative weight at 1500 and 3000 ppm from day 3 onwards in both sexes, with an increase in relative liver weight being also observed in male rats given 250 ppm fluxapyroxad for 14 days. Examination of liver sections revealed a centrilobular hepatocyte hypertrophy in some fluxapyroxad treated male and female rats. Hepatocyte replicative DNA synthesis (RDS) was significantly increased in male rats given 1500 and 3000 ppm fluxapyroxad for 3 and 7 days and in female rats given 50–3000 ppm fluxapyroxad for 7 days and 250–3000 ppm fluxapyroxad for 3 and 14 days; the maximal increases in RDS in both sexes being observed after 7 days treatment. The treatment of male and female Wistar rats with 250–3000 ppm fluxapyroxad for 14 days resulted in significant increases in hepatic microsomal total cytochrome P450 (CYP) content and CYP2B subfamily-dependent enzyme activities. Male Wistar rat hepatocytes were treated with control medium and medium containing 1–100 μM fluxapyroxad or 500 μM sodium phenobarbital (NaPB) for 4 days. Treatment with fluxapyroxad and NaPB increased CYP2B and CYP3A enzyme activities and mRNA levels but had little effect on markers of CYP1A and CYP4A subfamily enzymes and of the peroxisomal fatty acid β-oxidation cycle. Hepatocyte RDS was significantly increased by treatment with fluxapyroxad, NaPB and 25 ng/ml epidermal growth factor (EGF). The treatment of hepatocytes from two male human donors with 1–100 μM fluxapyroxad or 500 μM NaPB for 4 days resulted in some increases in CYP2B and CYP3A enzyme activities and CYP mRNA levels but had no effect on hepatocyte RDS, whereas treatment with EGF resulted in significant increase in RDS in both human hepatocyte preparations. Hepatocytes from male Sprague-Dawley wild type (WT) and constitutive androstane receptor (CAR) knockout (CAR KO) rats were treated with control medium and medium containing 1–16 μM fluxapyroxad or 500 μM NaPB for 4 days. While both fluxapyroxad and NaPB increased CYP2B enzyme activities and mRNA levels in WT hepatocytes, only minor effects were observed in CAR KO rat hepatocytes. Treatment with both fluxapyroxad and NaPB only increased RDS in WT and not in CAR KO rat hepatocytes, whereas treatment with EGF increased RDS in both WT and CAR KO rat hepatocytes. In conclusion, a series of in vivo and in vitro investigative studies have demonstrated that fluxapyroxad is a CAR activator in rat liver, with similar properties to the prototypical CAR activator phenobarbital. A robust MOA for fluxapyroxad-induced rat liver tumour formation has been established. Based on the lack of effect of fluxapyroxad on RDS in human hepatocytes, it is considered that the MOA for fluxapyroxad-induced liver tumour formation is qualitatively not plausible for humans.

Bibliometric Analysis of Scientific Publications on Communicative Behavior Problems

Purpose of research. The purpose of the study is to analyze the dynamics of the publication activity of scientific research in the field of studying communicative behavior. Communicative behavior is an object with an interdisciplinary research status. It falls into the area of research interest of various scientific fields. A bibliometric analysis of publication activity was carried out in connection with solving several tasks: to find out areas of knowledge in which the greatest publication activity is concentrated, to study the methods that are used in various fields of communicative behavior analysis, to identify organizations that are included in this research search.Methods. The study was conducted in two scientific electronic databases: the Russian Scientific Electronic Library Elibrary.ru and the international open platform for researchers and scientific organizations Lens. The bibliometric analysis was used as the research method. It involves the quantification of documentary information flows and it is based on quantitative research indicators reflecting the state of science as a whole or its individual branches.Results. As a result of the bibliometric analysis of publication activity on the problems of scientific research in the field of communicative behavior, communicative behavior in the digital environment and communicative behavior in social networks, a significant increase in publication activity was revealed in both international and Russian information databases over the past 10 years (2013 - 2023). It is also noted that the predominant number of publications on the issues studied is concentrated in the field of psychology. However, we can trace a shift in the focus of foreign research on communicative behavior towards digitalization in information technology, and Russian research towards the field of digital technologies in the educational environment.Conclusion. The results obtained indicate the high relevance, as well as the scientific and practical significance of the research topic on the problems of communicative behavior in general, as well as communicative behavior in the digital environment and social networks, in particular.

Empagliflozin inhibits increased Na influx in atrial cardiomyocytes of patients with HFpEF.

Heart failure with preserved ejection fraction (HFpEF) causes substantial morbidity and mortality. Importantly, atrial remodeling and atrial fibrillation is frequently observed in HFpEF. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have recently been shown to improve clinical outcomes in HFpEF, and post-hoc analyses suggest atrial antiarrhythmic effects. We tested if isolated human atrial cardiomyocytes from patients with HFpEF exhibit an increased Na influx, which is known to cause atrial arrhythmias, and if that is responsive to treatment with the SGTL2i empagliflozin. Cardiomyocytes were isolated from atrial biopsies of 124 patients (82 with HFpEF) undergoing elective cardiac surgery. Na influx was measured with the Na-dye Asante Natrium Green-2 AM (ANG-2). Compared to patients without heart failure (NF), Na influx was doubled in HFpEF patients (NF vs HFpEF: 0.21±0.02 vs 0.38±0.04 mmol/L/min (N=7 vs 18); p=0.0078). Moreover, late INa (measured via whole-cell patch clamp) was significantly increased in HFpEF compared to NF. Western blot and HDAC4 pulldown assay indicated a significant increase in CaMKII expression, CaMKII autophosphorylation, CaMKII activity, and CaMKII-dependent NaV1.5 phosphorylation in HFpEF compared to NF, whereas NaV1.5 protein and mRNA abundance remained unchanged. Consistently, increased Na influx was significantly reduced by treatment with the CaMKII inhibitor autocamtide-2 related inhibitory peptide (AIP), late INa inhibitor tetrodotoxin (TTX) but also with NHE1 inhibitor cariporide. Importantly, empagliflozin abolished both increased Na influx and late INa in HFpEF. Multivariate linear regression analysis, adjusting for important clinical confounders, revealed HFpEF to be an independent predictor for changes in Na handling in atrial cardiomyocytes. We show for the first time increased Na influx in human atrial cardiomyocytes from HFpEF patients, partly due to increased late INa and enhanced NHE1-mediated Na influx. Empagliflozin inhibits Na influx and late INa, which could contribute to antiarrhythmic effects in patients with HFpEF.