Impact of pre-operative weight loss on non-alcoholic fatty liver disease histopathology and insulin resistance in individuals undergoing bariatric surgery: a propensity matched cross-sectional comparison.

BACKGROUND: The effect of weight loss (WL) on histopathological aspects of non-alcoholic fatty liver disease (NAFLD) may provide further insights into the dynamics of hepatic recovery after WL. OBJECTIVE: To analyze the effects of pre-operative WL on insulin resistance- and NAFLD-related histology in individuals undergoing bariatric surgery (BS) with or without pre-operative WL. DESIGN AND SETTING: A matched cross-sectional study was conducted at a public university hospital and a private clinic in Campinas, Brazil. METHODS: An analytical, observational, cross-sectional study was conducted using prospectively collected databases of individuals who underwent BS and liver biopsy at either a public tertiary university hospital (with pre-operative WL) or a private clinic (without pre-operative WL). Random electronic matching by gender, age, and body mass index (BMI) was performed and two paired groups of 24 individuals each were selected. RESULTS: Of the 48 participants, 75% were female. The mean age was 37.4 ± 9.6. The mean BMI was 38.9 ± 2.6 kg/m2. Fibrosis was the most common histopathological abnormality (91.7%). Glucose was significantly lower in the WL group (92 ± 19.1 versus 111.8 ± 35.4 mg/dL; P = 0.02). Significantly lower frequencies of macrovesicular steatosis (58.3% versus 95.8%; P = 0.004), microvesicular steatosis (12.5% versus 87.5%; P < 0.001), and portal inflammation (50% versus 87.5%; P = 0.011) were observed in the WL group. CONCLUSION: Pre-operative WL was significantly associated with lower frequencies of macro- and mi- crovesicular steatosis, portal inflammation, and lower glycemia, indicating an association between the recent trajectory of body weight and histological aspects of NAFLD.

Translation, cross-cultural adaptation, and validation of health and self-management in diabetes questionnaire (HASMID-10) into Brazilian Portuguese.

BACKGROUND: Considering the ability of the health and self-management in diabetes questionnaire (HASMID-10) to verify the impact of self-management on diabetes, we highlight its relevance to scientific research and clinical applicability. However, to date, no study has been conducted to scientifically support its use in other languages. OBJECTIVE: To translate, cross-culturally adapt, and validate the HASMID-10 into the Brazilian Portuguese. DESIGN AND SETTING: A translation, cross-cultural adaptation, and validation study conducted at Ceuma University. METHODS: Study was conducted in accordance with the Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and Consensus-based Standards for the Selection of Health Measurement Instruments. We included participants of both sexes diagnosed with diabetes, aged between 18 and 64 years, and without cognitive deficits or any other limitations that would prevent them from answering the questionnaire. We assessed participants using the problem areas in diabetes (PAID) scale and HASMID-10. We assessed reliability using a test-retest model with a 7-day interval between assessments. We used intraclass correlation coefficient (ICC), 95% confidence interval (CI), standard error of measurement (SEM), minimum detectable difference (MDD), Spearman correlation coefficient, and floor and ceiling effects. RESULTS: Sample comprised 116 participants, most of whom were women, overweight, non-practitioners of physical activity, and nonsmokers. We observed significant correlations (P = 0.006; rho = -0.256) between the HASMID-10 and PAID, adequate reliability (ICC = 0.780) and internal consistency (Cronbach's alpha = 0.796). No ceiling or floor effects were observed. CONCLUSION: HASMID-10 has adequate measurement properties and may be used for Brazilians.

Monitoring the feeding and parental care behavior of a pair of free-living owls (Tyto furcata) in the nest during the reproductive period in Rio de Janeiro, Brazil / Monitoramento do comportamento alimentar e cuidado parental de um casal de corujas de vida livre (Tyto furcata) no ninho durante o período reprodutivo no Rio de Janeiro, Brasil

Abstract The American Barn Owl (Tyto furcata) lives in urban, periurban and wild environments and feeds mainly on small rodents, meaning it has great importance in the biological control of pests. The aim of this work was to describe the reproductive, parental and eating habits of a pair of American barn owls naturally living outside a residence in the urban area of the municipality of Campos dos Goytacazes, Rio de Janeiro state, Brazil. A wood box was installed on an outside wall of the home, monitored by a video camera. A spreadsheet was created to keep track of the observations recorded. The female laid four eggs, and after an incubation period of 30-32 days all the eggs hatched, but only two chicks survived after cannibalism among the chicks. Initially, the male provided the food to the chicks and the female remained in the nest caring for the brood. After approximately a month, the female also began to leave the nest and return with prey, which was offered to the chicks, with the male also continuing this behavior. The chicks left the nest in September, 2017. The data obtained show the existence of cooperation and division of tasks between male and female owls during the reproductive period.

Resumo A coruja-das-torres americana (Tyto furcata) vive em ambientes urbanos e se alimenta principalmente de pequenos roedores, sendo de grande importância no controle biológico de pragas. O objetivo deste trabalho foi descrever os hábitos alimentares, parentais e reprodutivos de um casal de corujas-das-torres americanas, naturalmente vivendo fora de uma residência na zona urbana do município de Campos dos Goytacazes, estado do Rio de Janeiro, Brasil. Uma caixa de madeira foi instalada em uma parede externa da casa, monitorada por uma câmera de vídeo. Uma planilha foi criada para manter o controle das observações registradas. A fêmea pôs quatro ovos, e após período de incubação de 30-32 dias todos os ovos eclodiram, mas apenas dois filhotes sobreviveram após o canibalismo entre os filhotes. Inicialmente, o macho fornecia a comida aos filhotes e a fêmea permanecia no ninho cuidando da ninhada. Depois de cerca de um mês, a fêmea também começou a sair do ninho e voltar com a presa, que era oferecida aos filhotes, com o macho também continuando com esse comportamento. Os filhotes deixaram o ninho em setembro de 2017. Os dados obtidos mostram a existência de cooperação e divisão de tarefas entre corujas machos e fêmeas durante o período reprodutivo.

Prediction of visceral leishmaniasis incidence using the Seasonal Autoregressive Integrated Moving Average model (SARIMA) in the state of Maranhão, Brazil / Previsão da incidência da leishmaniose visceral usando o modelo de média móvel integrado autorregressivo sazonal (SARIMA) no Maranhão, Brasil

Abstract Visceral leishmaniasis (VL) is an infectious disease predominant in countries located in the tropics. The prediction of occurrence of infectious diseases through epidemiologic modeling has revealed to be an important tool in the understanding of its occurrence dynamic. The objective of this study was to develop a forecasting model for the incidence of VL in Maranhão using the Seasonal Autoregressive Integrated Moving Average model (SARIMA). We collected monthly data regarding VL cases from the National Disease Notification System (SINAN) corresponding to the period between 2001 and 2018. The Box-Jenkins method was applied in order to adjust a SARIMA prediction model for VL general incidence and by sex (male or female) for the period between January 2019 and December 2013. For 216 months of this time series, 10,431 cases of VL were notified in Maranhão, with an average of 579 cases per year. With regard to age range, there was a higher incidence among the pediatric public (0 to 14 years of age). There was a predominance in male cases, 6437 (61.71%). The Box-Pierce test figures for overall, male and female genders supported by the results of the Ljung-Box test suggest that the autocorrelations of residual values act as white noise. Regarding monthly occurrences in general and by gender, the SARIMA models (2,0,0) (2,0,0), (0,1,1) (0,1,1) and (0,1,1) (2, 0, 0) were the ones that mostly adjusted to the data respectively. The model SARIMA has proven to be an adequate tool for predicting and analyzing the trends in VL incidence in Maranhão. The time variation determination and its prediction are decisive in providing guidance in health measure intervention.

Resumo A leishmaniose visceral (LV) é uma doença de natureza infecciosa, predominante em países de zonas tropicais. A predição de ocorrência de doenças infecciosas através da modelagem epidemiológica tem se revelado uma importante ferramenta no entendimento de sua dinâmica de ocorrência. O objetivo deste estudo foi desenvolver um modelo de previsão da incidência da LV no Maranhão usando o modelo de Média Móvel Integrada Autocorrelacionada Sazonal (SARIMA). Foram coletados os dados mensais de casos de LV através do Sistema de Informação de Agravos de Notificação (SINAN) correspondentes ao período de 2001 a 2018. O método de Box-Jenkins foi aplicado para ajustar um modelo de predição SARIMA para incidência geral e por sexo (masculino e feminino) de LV para o período de janeiro de 2019 a dezembro de 2023. Durante o período de 216 meses dessa série temporal, foram registrados 10.431 casos de LV no Maranhão, com uma média de 579 casos por ano. Em relação à faixa etária, houve maior registro no público pediátrico (0 a 14 anos). Houve predominância do sexo masculino, com 6437 casos (61,71%). Os valores do teste de Box-Pierce para incidência geral, sexo masculino e feminino reforçados pelos resultados do teste Ljung-Box sugerem que as autocorrelações de resíduos apresentam um comportamento de ruído branco. Para incidência mensal geral e por sexo masculino e feminino, os modelos SARIMA (2,0,0) (2,0,0), (0,1,1) (0,1,1) e (0,1,1) (2, 0, 0) foram os que mais se ajustaram aos dados, respectivamente. O modelo SARIMA se mostrou uma ferramenta adequada de previsão e análise da tendência de incidência da LV no Maranhão. A determinação da variação temporal e sua predição são determinantes no norteamento de medidas de intervenção em saúde.

Effects of Pasturella Multocida B: 2 and its immunogens (LPS and OMP) on reproductive hormones in Nili-Ravi Buffaloes / Efeitos de Pasteurella multocida B: 2 e seus imunógenos (LPS e OMP) em hormônios reprodutivos em búfalos Nili-Ravi

Abstract Livestock is a fundamental part of the agriculture industry in Pakistan and contributes more than 11.53% to GDP. Among livestock species, the buffaloes are regarded as the black gold of Pakistan. Being the highest milk producers globally, Nili-Ravi buffaloes are the most famous ones. Buffaloes are affected by many endemic diseases, and "Hemorrhagic septicemia" (HS) is one of them. This study was designed to ascertain the effects of experimental exposure ofP. multocida B:2 (oral) and its immunogens, i.e., LPS (oral and intravenous) and OMP (oral and subcutaneous) on reproductive hormonal profiles in Nili-Ravi buffaloes. Repeated serum samples were collected from the jugular vein of experimental animals for 21 days (0, 02, 04, 08, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 and 504 hours). Hormonal assays to determine the serum concentrations of Gonadotropin-releasing hormone (GnRH), Follicle-stimulating hormone (FSH), Luteinizing hormone (LH), Estrogen (E2) and progesterone (P4) were performed using (MyBioSource) commercial Elisa kits. The hormonal profile of all treatment groups of the buffalo heifers exhibited significant (P<0.05) variations as compared to the control group (G-1). These results indicate suppression in Nili-Ravi buffaloes' reproductive hormonal profile on exposure to P. multocida B:2 and its immunogens. This influence warrants that exposure to H.S may be a possible reason for delayed puberty and poor reproduction performance in Nili-Ravi buffaloes.

Resumo A pecuária é uma parte fundamental da indústria agrícola no Paquistão e contribui com 11,53% do PIB nacional. Entre as espécies de gado, os búfalos são considerados o ouro negro do Paquistão. Sendo os maiores produtores de leite em todo o mundo, os búfalos Nili-Ravi são os mais famosos. Os búfalos são afetados por muitas doenças endêmicas, entre as quais a "septicemia hemorrágica" (SH). Este estudo busca verificar os efeitos da exposição experimental de P. multocida B:2 (oral) e seus imunógenos, ou seja, LPS (oral e intravenoso) e OMP (oral e subcutâneo), nos perfis hormonais reprodutivos em búfalos Nili-Ravi. Amostras de soro repetidas foram coletadas da veia jugular de animais experimentais por 21 dias (0, 2, 4, 8, 12, 16, 20, 24, 36, 48, 72, 120, 168, 216, 264, 360, 456 e 504 horas). Os ensaios hormonais para determinar as concentrações séricas do hormônio liberador de gonadotrofina (GnRH), hormônio foliculoestimulante (FSH), hormônio luteinizante (LH), estrogênio (E2) e progesterona (P4) foram realizados usando kits comerciais Elisa (MyBioSource). O perfil hormonal de todos os grupos de tratamento das novilhas bubalinas apresentou variações significativas (P < 0,05) em relação ao grupo controle (G-1). Esses resultados indicam supressão no perfil hormonal reprodutivo de búfalos Nili-Ravi na exposição a P. multocida B:2 e seus imunógenos. Essa influência garante que a exposição à SH possa ser uma possível razão para o atraso da puberdade e o baixo desempenho reprodutivo em búfalos Nili-Ravi.

Quality of life of women from a quilombola community in northeastern Brazil / Qualidade de vida de mulheres de uma comunidade quilombola do nordeste brasileiro

Abstract Quilombola communities are present in many Brazilian states living in precarious health conditions. This is due to geographic isolation, limitations to the access of the area in which they live in, and the lack of quality in the service when it is needed to be provided. Therefore, the aim of this study was to analyze the quality of life of women from a quilombola community in northeastern Brazil. It is an observational, cross-sectional and descriptive study. 160 adult women were first interviewed through a form to collect a profile and then it was applied the WHOQOL Quality of Life questionnaire - bref. It was observed that the women were on average 40.7 years old (±17.25), married, self-declared black, who did not finish elementary school, housewife, had no income, with their own masonry house, with up to 6 rooms, supplied by a box of community treated water. Quality of Life had median scores in the domains: physical (3.18), psychological (3.4), social relationships (3.45) and environment (2.59). With this research, it was possible to characterize the quilombola community of Santa Luzia do Norte-AL regarding the difficulties of access to health and income generation, issues that affect their health condition. The problems described in this study can contribute to health actions being planned and carried out in order to improve socioeconomic and health conditions in this community, considering the social, political and environmental context, valuing their traditional knowledge and practices.

Resumo As comunidades quilombolas, estão presentes em diversos estados brasileiros, vivendo em condições de saúde mais precárias. Isto ocorre por conta do isolamento geográfico, das limitações de acesso e da falta de qualidade no serviço quando este é prestado. Nesse sentido, o objetivo do estudo foi analisar a qualidade de vida de mulheres de uma comunidade quilombola do nordeste brasileiro. Estudo observacional, transversal e descritivo. Foram entrevistadas 160 mulheres adultas, através de um formulário para a coleta de perfil e do questionário de Qualidade de Vida WHOQOL - bref. Foi observado que as mulheres tinham em média 40,7 anos (±17,25), casadas, autodeclaradas negras, com fundamental incompleto, do lar, sem renda, com moradia de alvenaria, própria, com até 6 cômodos, abastecidas por caixa de água comunitária, tratada. A Qualidade de Vida, apresentou escores medianos nos domínios: físico (3,18), psicológico (3,4), relações sociais (3,45) e meio ambiente (2,59). Com a realização desta pesquisa foi possível caracterizar a comunidade quilombola de Santa Luzia do Norte-AL quanto as dificuldades de acesso a saúde e geração de renda, fatos que repercutem na sua condição de saúde. Os problemas descritos neste estudo podem contribuir para que ações de saúde sejam planejadas e efetivadas com o intuito de melhorar as condições socioeconômicas e de saúde nessa comunidade, considerando-se o contexto social, político e ambiental, valorizando seus saberes e práticas tradicionais.

Evaluation of Group Genetic Counseling Sessions via a Metaverse-based Application.

Background: Group genetic counseling has been implemented to meet growing demand. A metaverse platform, in which a society is built and activities are carried out in the virtual world, has not yet been implemented in group genetic counseling. We investigated whether a metaverse platform could be an alternative service-delivery model for group genetic counseling. Methods: Participants (N=131) were divided into three groups: patient (N=45), family (N= 43), and interested (N=43) groups. Participants entered the metaverse through a link sent to their mobile phones and attended a 20-min group genetic counseling session reviewing hereditary breast cancer, followed by a 10-min question-and-answer period. Results: The overall median score of post-educational knowledge (9.0, range 8.0-10.0) significantly increased compared to that of pre-educational knowledge (6.0, range 3.0-8.0) (P<0.001). There was no significant difference in the pre- and post-educational knowledge scores among the three groups (P>0.05). Most participants (95%) responded that their understanding of hereditary breast cancer had increased after the group genetic counseling session and that their satisfaction was high. The main advantage noted with metaverse was no limit of space and location while attending the session (97%), and the main disadvantage was a possibility of missing content due to an unstable internet connection (67%). Conclusions: The metaverse platform would be acceptable as an alternative group genetic counseling service. More studies are needed to investigate how, for whom, and in what circumstances metaverse can be effectively utilized.

Bacterial, short-chain fatty acid and gas profiles of partially hydrolyzed guar gum in vitro fermentation by human fecal microbiota.

Carbohydrates with different structures have metabolic differences in the human body, as well as individual differences. The present study aimed to investigate the effects of bacterial, short-chain fatty acids (SCFAs) and gas profiles of partially hydrolyzed guar gum (PHGG) on the fecal microbiota of 41 Chinese individuals by simulated fermentation in vitro. Results showed that PHGG stimulated the growth of Bifidobacterium and Faecalibacterium, inhibited the growth of Escherichia-Shigella, Klebsiella, and Dorea, and induced the production of fermentation gases (CO2, and H2) and SCFAs (acetic acid, butyric acid). Furthermore, Bifidobacterium was significantly increased in the young female and the old male-originated samples, while Klebsiella was significantly decreased in the old female ones after PHGG intervention, and there were also certain differences in gases and SCFAs among different population samples. These findings indicate that PHGG can modulate gut microbiota and metabolism well, whereas its use varies in different populations.

Dietary supplementation with synthetic astaxanthin and DHA interactively regulates physiological metabolism to improve the color and odor quality of ovaries in adult female Eriocheir sinensis.

The present study aimed to investigate the interactive effects of dietary supplementation to the feed with astaxanthin and/or DHA on the color and odor of Eriocheir sinensis ovaries. The results revealed that astaxanthin supplementation significantly increased redness of E. sinensis ovaries (P < 0.05). Moreover, the addition of either astaxanthin or DHA alone to the feed affected the deposition of carotenoids and fatty acids in E. sinensis ovaries. More importantly, the simultaneous supplementation of astaxanthin and DHA significantly improved color, carotenoid content, and polyunsaturated fatty acid content (P < 0.05) in E. sinensis ovaries, as well as increased the content of aroma compounds during thermal processing. Based on the present findings, the optimal combination of dietary astaxanthin and DHA is 100 mg/kg of synthetic astaxanthin and 0.15% of DHA, respectively, which could improve color and odor quality of ovaries for E. sinensis.

Label-Free quantitation of milk oligosaccharides from different mammal species and heat treatment influence.

Milk oligosaccharides (MOs) exhibit significant variations in concentrations and patterns among different species. However, there is limited knowledge about milk oligosaccharides in domestic animals and the impact of heat treatment on them. Here, we developed an LC-ESI-MS/MS method to analyze 11 milk oligosaccharides in 7 distinct species simultaneously. The results showed that human milk presented a completely different composition pattern of milk oligosaccharides from animals. In detail, animal milk predominantly contained sialylated oligosaccharides, and human milk had high levels of fucosylated neutral oligosaccharides. Notably, sheep milk exhibited similarities to human milk in terms of oligosaccharides composition. Then, the milk samples from dairy cows were treated with two common industrial heat treatments. We found that 65 °C treatment had no significant effect on the concentration of milk oligosaccharides, whereas 135 °C heating was associated with their decline, suggesting that high temperatures should be avoided in the processing of oligosaccharides supplemented/enriched products.

Effect of Muscle Forces on Femur During Level Walking Using a Virtual Population of Older Women.

Aging is associated with a greater risk of muscle and bone disorders such as sarcopenia and osteoporosis. These conditions substantially affect one's mobility and quality of life. In the past, muscles and bones are often studied separately using generic or scaled information that are not personal-specific, nor are they representative of the large variations seen in the elderly population. Consequently, the mechanical interaction between the aged muscle and bone is not well understood, especially when carrying out daily activities. This study presents a coupling approach across the body and the organ level, using fully personal-specific musculoskeletal and finite element models in order to study femoral loading during level walking. Variations in lower limb muscle volume/force were examined using a virtual population. These muscle forces were then applied to the finite element model of the femur to study the variations in predicted strains. The study shows that effective coupling across two scales can be carried out to study the muscle-bone interaction in elderly women. The generation of a virtual population is a feasible approach to augment anatomical variations based on a small population that could mimic variations seen in a larger cohort. This is a valuable alternative to overcome the limitation or the need to collect dataset from a large population, which is both time and resource consuming.

HPC Framework for Performing in Silico Trials Using a 3D Virtual Human Cardiac Population as Means to Assess Drug-Induced Arrhythmic Risk.

Following the 3 R's principles of animal research-replacement, reduction, and refinement-a high-performance computational framework was produced to generate a platform to perform human cardiac in-silico clinical trials as means to assess the pro-arrhythmic risk after the administrations of one or combination of two potentially arrhythmic drugs. The drugs assessed in this study were hydroxychloroquine and azithromycin. The framework employs electrophysiology simulations on high-resolution three-dimensional, biventricular human heart anatomies including phenotypic variabilities, so as to determine if differential QT-prolongation responds to drugs as observed clinically. These simulations also reproduce sex-specific ionic channel characteristics. The derived changes in the pseudo-electrocardiograms, calcium concentrations, as well as activation patterns within 3D geometries were evaluated for signs of induced arrhythmia. The virtual subjects could be evaluated at two different cycle lengths: at a normal heart rate and at a heart rate associated with stress as means to analyze the proarrhythmic risks after the administrations of hydroxychloroquine and azithromycin. Additionally, a series of experiments performed on reanimated swine hearts utilizing Visible Heart® methodologies in a four-chamber working heart model were performed to verify the arrhythmic behaviors observed in the in silico trials.The obtained results indicated similar pro-arrhythmic risk assessments within the virtual population as compared to published clinical trials (21% clinical risk vs 21.8% in silico trial risk). Evidence of transmurally heterogeneous action potential prolongations after providing a large dose of hydroxychloroquine was found as the observed mechanisms for elicited arrhythmias, both in the in vitro and the in silico models. The proposed workflow for in silico clinical drug cardiotoxicity trials allows for reproducing the complex behavior of cardiac electrophysiology in a varied population, in a matter of a few days as compared to the months or years it requires for most in vivo human clinical trials. Importantly, our results provided evidence of the common phenotype variants that produce distinct drug-induced arrhythmogenic outcomes.

Efficacy and safety of Chinese patent medicine paiteling in condyloma acuminatum: A systematic review and meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Condyloma acuminatum (CA) is a common sexually transmitted disease. Previous studies using randomized controlled trials (RCTs) have revealed that Paiteling (PTL), a Chinese patent medicine formula, can effectively relieve CA symptoms. However, the evidence needs to be more cohesive and there is a need for a clear summary of the existing RCTs to assess the overall efficacy and safety profile of PTL. AIMS OF THE STUDY: This study aimed to conduct a comprehensive review and meta-analysis of RCTs, to examine the efficacy of PTL and physical therapies in CA. MATERIAL AND METHODS: A literature search was conducted in multiple databases, including PubMed, MEDLINE, Cochrane Library, etc. up to December 1, 2022. Revman 5.4 and Stata 15.0 was used for data statistics and sensitivity analyses. RESULTS: 31 trials with a total of 2868 patients were included in this review. The results showed that PTL plus physical therapies were significantly more effective than physical therapies used alone (RR = 1.60, 95% CI [1.38, 1.86]; P < 0.00001). Subgroup analysis showed that the type of physical therapies, gender, and wart location might be the primary sources of heterogeneity. Additionally, PTL can reduce recurrence rates (RR = 0.27, 95% CI [0.19, 0.39]; P < 0.00001), improve the negative conversion rate of HPV (RR = 1.15, 95% CI [1.02, 1.30]; P = 0.02), and improve immune function. No severe adverse reactions or physical injuries were observed, making it a better choice for women planning to become pregnant. CONCLUSION: Compared with physical therapies, PTL can effectively eliminate CA symptoms and reduce the recurrence rates with safety ensured. However, due to the heterogeneity and methodological shortcomings, large sample sizes and high-quality rigorous RTCs are still needed to strengthen this clinical evidence.

A blend of Withania somnifera (L.) Dunal root and Abelmoschus esculentus (L.) Moench fruit extracts relieves constipation and improves bowel function: A proof-of-concept clinical investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Withania somnifera (L.) Dunal (WS) and Abelmoschus esculentus (L.) Moench (AE) are known as Ashwagandha and Okra, respectively, important herbs in traditional medicine for their diverse therapeutic values. WS root is an adaptogen that relieves stress and anxiety and promotes sleep. AE fruit or Okra is widely consumed as a vegetable and is traditionally used to treat diabetes, gastric irritations, ulcers, and obesity. AIM OF THE STUDY: The present randomized, double-blind, placebo-controlled study aimed to establish a proof-of-concept evaluating the efficacy and tolerability of a proprietary blend of standardized extracts of WS root and AE fruit, CL18100F4 in relieving constipation and improving quality of life in adults. MATERIALS AND METHODS: Forty-eight male and female participants (age: 25-60 years) with functional constipation (following Rome-III criteria) were randomized into placebo, 300 or 500 mg of CL18100F4 groups, and supplemented for fourteen consecutive days. RESULTS: CL18100F4 supplementation significantly (p < 0.0001) reduced the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), and Gastrointestinal Symptom Rating Scale (GSRS) scores. CL18100F4 supplementation improved sleep quality and reduced stress (p < 0.0001). At the end of the study, CL18100F4-500 subjects showed significant increases in serum serotonin, gastrin, and interleukin-10 and decrease in interleukin-6 and cortisol levels. Participants' hematology, total blood chemistry, vital signs, and urinalysis parameters were within the normal ranges. No adverse events were reported. CONCLUSIONS: This short-duration, single-site clinical investigation demonstrates that CL18100F4 supplementation is tolerable, helps relieve constipation, reduces stress, and improves gastrointestinal function, sleep quality, and general wellness in adults. TRIAL REGISTRATION: Clinical Trials Registry- India (CTRI/2020/11/029320); Registered on 24/11/2020. Available at: http://ctri.nic.in/Clinicaltrials/showallp.php?mid1=49391&EncHid=&userName=CL18100F4.

Network pharmacology and experimental validation on yangjing zhongyu decoction against diminished ovarian reserve.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) was considered a refractory reproductive endocrine condition that negatively affected female reproductivity. Yangjing Zhongyu Decoction (YJZYD) had effects on treating infertility. However, there were few studies on the mechanisms of YJZYD preserving ovarian reserve. AIM OF THE STUDY: To explore the possible mechanisms of YJZYD against DOR by UPLC-ESI-MS/MS, network pharmacology, and experimental validation. METHODS: The chemicals of YJZYD were measured by UPLC-ESI-MS/MS. The correlating targets of YJZYD and DOR were identified by the ETCM database, GeneCards database, and PubMed database. The common targets were employed with the DAVID database and visualized with the PPI network. GO and KEGG enrichment analyses were carried out to explore biological progression and pathways. In vivo experiments, energy production was assessed by ATP, and apoptosis rate was analyzed by TUNEL. The serum FSH, AMH, and E2 levels were evaluated by ELISA. Western blotting and immunohistochemistry were used to measure the expression of SIRT1, PGC1α, NRF1, COX IV, FSHR, CYP19A1, PI3K, p-Akt, Akt, Bcl-2, and Bax. RESULTS: 132 components in YJZYD were identified by UPLC-ESI-MS/MS. 149 overlapped targets were extracted from YJZYD and DOR, and the top 20 common targets included AKT1 and CYP19A1. ATP binding was involved in GO analysis. In the KEGG enrichment analysis, the metabolic pathway was the top, and the PI3K-Akt signaling pathway was included. In vivo experiments, YJZYD improved ovarian index and histomorphology. After YJZYD treatment, serum FSH, E2, and AMH were well-modulated, and the content of ATP was up-regulated. Besides, the expression of Bax was suppressed in ovarian tissue, while the expressions of SIRT1, PGC1α, NRF1, COX IV, FSHR, CYP19A1, PI3K, Bcl-2, and p-Akt/Akt were enhanced. CONCLUSION: YJZYD could attenuate reproductive endocrine disturbance and ovarian lesions in vivo by mediating steroidogenesis, energy metabolism, and cell apoptosis. This study uncovered the mechanisms of YJZYD against DOR, providing a theoretical basis for further study.

Chinese herbal medicine alleviates autophagy and apoptosis in ovarian granulosa cells induced by testosterone through PI3K/AKT1/FOXO1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine and metabolic disorder. Chinese herbal medicine has some advantages in the treatment of PCOS with its unique theoretical system and rich clinical practice experiences. AIM OF THE STUDY: The present study was to investigate the potential mechanisms of Bu-Shen-Jian-Pi Formula (BSJPF) on the treatment of PCOS. MATERIAL AND METHODS: The combination of ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS/MS) rapid analysis, network pharmacology, molecular docking analysis and bio-experiments were firstly conducted to identify the main effective components of BSJPF, and to predict the potential mechanisms. The ovarian granulosa cell line (KGN) was treated with testosterone to construct the PCOS model in vitro, and the cells were further treated with the lyophilized powder of BSJPF. The levels of proliferation, autophagy and apoptosis were detected to explore the mechanisms of BSJPF on treating PCOS. RESULTS: Firstly, thirty-six active compounds were identified in BSJPF and thirty-one potential targets on PCOS were found. Then, PI3K and PDK1 were verified to have good binding activity with the active compounds through molecular docking analysis. In bio-experiments, BSJPF significantly alleviated the arrested proliferation of KGN cells in G0/G1 phase and reduced the active levels of autophagy and apoptosis of KGN cells induced by testosterone. Additionally, the inhibition of autophagy diminished apoptosis, while the repression apoptosis enhanced autophagy. Finally, BSJPF significantly decreased the FOXO1 expression levels induced by testosterone, especially for nuclear FOXO1, and significantly activated the PI3K/AKT pathway. CONCLUSIONS: BSJPF significantly alleviated the activated autophagy and apoptosis in KGN induced by testosterone through PI3K/AKT1/FOXO1pathway, which is an effective treatment for PCOS.

Oliveria decumbens Vent. (Apiaceae): Biological screening and chemical compositions.

ETHNOPHARMACOLOGICAL RELEVANCE: Oliveria decumbens Vent. (Apiaceae), a single aromatic species in Iran, is traditionally used for healing inflammation, gastrointestinal disorders, and infections. AIM OF THE STUDY: Regarding the importance of O. decumbens in traditional medicine, we aimed to set out the plant's biological screening and analyze the chemical components of the active fractions. MATERIALS AND METHODS: Air-dried O. decumbens aerial parts were macerated by ethanol:water (70:30). Using a liquid-liquid extraction (LLE) technique, n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and water were successively used to fractionate the crude extract into different portions. Various biological activities were performed on the crude extract, fractions, and some experiments on pure compounds. The bioassays were as follows: antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Salmonella typhi (using microplate alamar blue assay; MABA), antifungal activity against Aspergillus niger, A. fumigatus, Candida albicans, C. glabarate, Fusarium lini, Microspurum canis, and Trichophyton rubrum (using agar tube dilution method), antileishmanial activity against Leishmania major and L. tropica using a 96-well serial dilution protocol, anti-inflammatory activity using the respiratory burst assay, cytotoxicity against HeLa (cervical cancer) and BJ (normal fibroblast) cells using MTT assay, insecticidal activity against Tribolium castaneum, Sitophilus oryzae, and Rhyzopertha dominica (using the contact toxicity method), larvicidal activity against Aedes aegypti, anti-DPPH• activity, and cytotoxicity against brine shrimp (Artemia salina) in a lethality assay. Eventually, the phytochemicals from the active fractions were studied by gas chromatography coupled with mass spectrometry (GC-MS). RESULTS: Interestingly, the DCM fraction was the most active, followed by the n-hexane fraction in the biological assays, including antibacterial (>80% inhibition), leishmanicidal (IC50 (L.major) = 29.4 µg/mL, and IC50 (L.tropica) = 30.0 µg/mL), anti-inflammatory (IC50 = 15.8 µg/mL), insecticidal (>80% inhibition), and larvicidal (100% inhibition of A. aegypti) assays. Further GC-MS analysis of the DCM and n-hexane fractions resulted in the characterization of 12 and 14 phytoconstituents, respectively, compared with the NIST library. Thymol and carvacrol were abundant in both fractions. To lesser quantities, the presence of monoterpenoids (p-cymen-8-ol, thymoquinone, 3-hydroxy-ß-damascone, and 3-hydroxy-7,8-dihydro-ß-ionol), phenylpropanoids (methoxyeugenol, elemicin, and 4-[(1E)-3-hydroxy-1-propenyl]-2-methoxyphanol, simple phenolics (salicylic acid and 4-methoxy-2,3,6-trimethyl-phenol), and a coumarin (6,7-dimethoxy-coumarin) were detected in the DCM fraction. On the other hand, besides a coumarin and monoterpenoids, the fatty acids (tetradecanoid acid, n-hexadecanoic acid, and linolenic acid) and a sesquiterpene (spathulenol) were observed in the n-hexane fraction. The EtOAc fraction scavenged the DPPH• radicals better than other fractions (IC50 = 41.4 µg/mL), while in brine shrimp lethality assay, the crude extract was more active than n-hexane and DCM fractions with LD50 = 385.20, 660.28, and 699.74 µg/mL, respectively. Surprisingly, the crude extract and fractions were ineffective against assayed fungal strains and tested cancer and non-cancer cell lines. CONCLUSIONS: Our findings showed that O. decumbens deserves to be a multi-bioactive medicinal plant, besides its ability for cereal protection against pests. To understand the principal mechanism of action, in silico, in vitro, and in vivo experiments may clarify the ambiguities and even figure out the synergistic behavior of the minor secondary metabolites.

Anti-inflammatory effects of Arnica montana (mother tincture and homeopathic dilutions) in various cell models.

ETHNOPHARMACOLOGICAL RELEVANCE: The plant Arnica montana L. has been shown to alleviate inflammation, pain and swelling associated with trauma, and post-operative clinical conditions, yet the mechanism of action is not well understood. AIM OF THE STUDY: The study was designed to investigate the effect of Arnica montana (A. montana) mother tincture and homeopathic dilutions on inflammation markers, oxidative stress and cell migration in diverse cell culture models. MATERIALS AND METHODS: We tested A. montana mother tincture and a range of homeopathic dilutions in different human and murine cell culture models to demonstrate their anti-inflammatory properties by measuring the inflammatory markers: tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule (ICAM-1), reactive oxygen species (ROS) and cell migration. The inflammatory markers were measured by ELISA assays. The intracellular oxidative stress (ROS) in microglial cells was measured using Deep Red CellROX probe. The cell migration was examined by wound healing using the Oris Cell migration assay. RESULTS: These data showed the ability of A. montana (mother tincture and mainly 1C dilution) to significantly reduce TNFα production in inflamed macrophages compared with vehicle (control). They significantly reduced both IL-6 and MCP-1 in inflamed human microglial cells and significantly decreased COX-2 expression in inflamed murine fibroblasts. Moreover, A. montana mother tincture reduced the cell migration whereas 9C dilution significantly enhanced the migration of fibroblast cells compared with vehicle. The expression of ICAM-1 was significantly reduced with A. montana mother tincture and 1C, 3C, 5C, and 9C dilutions in inflamed human endothelial cells compared with vehicle. A. montana mother tincture and 1C, 3C, 5C and 9C dilutions induced a significant and consistent effect on ROS production in inflamed murine microglial cells. A. montana 1C had the largest impact on ROS production. CONCLUSIONS: Mother tincture and 1C dilution of A. montana showed anti-inflammatory properties assessed by measurement of several markers (pro-inflammatory cytokines, adhesion molecule, ROS) in various human and murine cell models. In addition, A. montana 3C, 5C, 9C dilutions have anti-inflammatory and antioxidant effects as highlighted on both primary endothelial cells and murine microglial cells.

Sonocatalytic degrading antibiotics over activated carbon in cow milk.

Herein, an efficient, simple and economical approach to remove antibiotics (ABX), i.e. ceftiofur hydrochloride, sulfamonomethoxine sodium (SMM), marbofloxacin and oxytetracycline by sonication with activated carbon (AC) from cow milk has been successfully implemented. The pseudo-first-order kinetics constants for the sonolytic and sonocatalytic degrading SMM are 0.036 and 0.093 min-1, respectively. The synergistic efficiency of removing ABX by using sonocatalysis reached 1.8-4.0. Hydrophobic ABX underwent faster degradation than hydrophilic ABX in sonocatalytic systems. Adding 0.5 mmol L-1 H2O2, the optimal concentration, improved the sonocatalytic degradation rates of ABX by 9.1%-28.5%. Surface area and dose of AC play crucial roles in the sonocatalysis of ABX. By sonicating 50 mL of 5.52 µmol L-1 ABX in milk at 500 kHz and 259 W with 20 mg AC for 20-60 min resulted in residual ABX concentrations ranging from 42.6 to 95.1 µg L-1, which meet the relative maximum residue limits set by European Commission.

Liquid crystal biosensor based on AuNPs signal amplification for detection of human chorionic gonadotropin.

The detection of human chorionic gonadotropin (HCG) allows for the determination of pregnancy and is thus crucial during early pregnancy testing. This study introduces a novel liquid crystal (LC) biosensor that employs Au nanoparticles (AuNPs) for signal amplification, thus enabling the detection of the HCG antigen in a micro, efficient, and cost-effective manner. The sensor design capitalizes on the unique properties of LC to facilitate the detection of HCG. In this research, the surface of the base substrate was first modified with material from DMOAP and APTES, and EDC/sulfo-NHS was used to couple AuNPs and ß-hCG to form an AuNP-ß-hCG conjugate that improves the coupling rate. The carboxyl group of the antibody was reacted with the aldehyde group of glutaraldehyde, which helps to fix the ß-hCG antibody to the surface of the substrate. The HCG sample is immobilized on the surface of the substrate via antigen-antibody immunobinding. As signal amplifiers, the AuNPs can have a significant effect on the topology of the interface and the vertical order of the LC molecules, thus reducing the limit of detection. Finally, the limit of detection was calculated using the SPSS system, and the relationship between grey values and concentrations was also obtained. The detection limit for HCG can be as low as 1.916 × 10-3 mIU·mL-1 under ideal conditions. Compared to other detection methods for HCG, this structure provides a detection pathway with excellent sensitivity, low detection limits, and better specificity, thus offering a new idea for HCG or any other target requiring trace detection.