The ameliorative effects of curcumin nanomicelle on testicular damage in the mouse model of multiple sclerosis.

BACKGROUND: This study investigated the effect of curcumin nanomicelle (CUR-n) on the structure of testis tissue, the process of spermatogenesis, LH, FSH, testosterone, and oxidative stress in a model of multiple sclerosis. METHODS: Twenty-four male mice C57BL/6 were randomly allocated into 4 groups of 6 (1: group receiving 2% CPZ diet, 2: group receiving the diet of 2% CPZ + CUR-n with a dose of 50 mg/kg, 3: group receiving the diet of 2% CPZ + CUR-n with a dose of 100 mg/kg). The concentration of hormones (testosterone, LH and FSH), was measured by the special hormone assay ELISA kits. Measuring total antioxidant capacity (TAC) and Malondialdehyde (MDA) levels was done by spectrophotometry and calorimetric methods, respectively. Stereological analysis was done in order to explore the number of spermatogenesis cells, testis and sperm properties. RESULTS: The results indicated that CUR-n (100 mg/kg) significantly enhanced the concentration of LH, FSH, testosterone, and TAC but reduced MDA levels. It also notably increased the quantity of spermatogonia, spermatocyte, round spermatids, long spermatids and LCs, augmented testis weight and volume, and germinal epithelium volume, improved sperm count, morphology, viability, and motility. In addition, a considerable decrease in the amount of wrinkling and disruption of the germinal epithelium was observed after intervention with CUR-n (100 mg/kg). Furthermore, a significant increase in the number of germ cells compared to the group receiving CPZ was detected. CONCLUSION: This study proposes that CUR-n could be a therapeutic agent for decreasing the adverse effects of MS on testis.

Probiotics ameliorate endocrine disorders via modulating inflammatory pathways: a systematic review.

Probiotics has offered a new prospect to treat and manage a variety of endocrine disorders such as obesity, diabetes, non- alcoholic fatty liver disease and metabolic syndrome. The precise mechanisms by which probiotics exert their beneficial effects on endocrine disorders and its associated problems are still indecisive. It seems that regulating the immune system and suppressing pro-inflammatory pathways like tumor necrosis factor-α and interleukin-6 or triggering anti-inflammatory pathways like interleukin-4 and 10 may be one of the potential mechanisms in the managing of endocrine disorders. In this systematic review, we hypothesized that various probiotic strains (Lactobacillus, Biofidiobacteria, Streptococcus, Entrococcus, Clostridium, and Bacillus) alone or in combination with each other could manage endocrine disorders via modulating inflammatory pathways such as suppressing pro-inflammatory cytokines (IL-6, IL-12, TNF-α, TNF-ß, NFκB, and MCP-1), stimulating anti-inflammatory cytokines (IL-4,IL-6, IL-22, IL-23, IL-33, and TGF-ß) and maintaining other factors like C-reactive protein, Toll like receptors, LPS, and NK cells. Data source this search was performed in PubMed and Scopus. Both human and animal studies were included. Among more than 15,000 papers, 25 studies were identified as eligible for more assessments. Quality assessment of the studies was cheeked by two researchers independently by title and abstract screening, then article which have inclusion criteria were included, and data retrieved from the included full text studies as the authors had originally reported. Results specified that Lactobacillus has been the most widely used probiotic as well as which one exhibiting the extend of the therapeutic effects on endocrine disorders, especially obesity by modulating immune responses. Also, most studies have revealed that probiotics through suppressing pro-inflammatory pathways specially via reducing levels TNF-α cytokine exhibited protective or beneficial effects on endocrine diseases particularly obesity as well as through decreasing level of IL-6 induced therapeutic effects in diabetes. This systematic review suggests that probiotics could ameliorate endocrine disorders via their immunomodulatory effects.

The effect of BsmI (rs1544410) single nucleotide polymorphism of vitamin D receptor (VDR) on insulin resistance in healthy children and adolescents: a cross-sectional study.

The increasing prevalence of metabolic syndrome, type 2 diabetes, and insulin resistance are driven by complex interactions between genetic and environmental factors. One of the single nucleotide polymorphisms (SNPs) in the VDR gene associated with vitamin D levels is the rs1544410 SNP. This study examined the association of the rs1544410 polymorphism with insulin resistance to predict and screen for possible association with type 2 diabetes and target these individuals for appropriate treatment. This cross-sectional study examined 270 children and adolescents aged 9 to 18 years. Anthropometric and biochemical parameters were determined. Insulin resistance/sensitivity was determined using Quicki, HOMA-IR, MacAuley, Revised MacAuley, Bennetts, FIRI and insulin-to-glucose ratio. The BsmI single nucleotide polymorphism (rs1544410) was determined using the PCR-RFLP method after extracting DNA from peripheral blood collected from fasted subjects, and the resulting data were analyzed using SPSS software and statistical tests.According to linear regression analysis, a significant difference was found in Insulin to glucose ratio, FIRI and HOMA-IR indices between Bb / bb and BB genotypes and it was observed that individuals with BB genotype polymorphism of BsmI vitamin D receptor gene, after Adjustment of age, sex, BMI are at greater risk for insulin resistance and type 2 diabetes.This study demonstrated that those with the BB genotype of VDR BsmI polymorphism were at higher risk for insulin resistance and developing type 2 DM.

The ameliorating effect of limosilactobacillus fermentum and its supernatant postbiotic on cisplatin-induced chronic kidney disease in an animal model.

BACKGROUND: Chronic kidney disease (CKD) is a worldwide public health problem affecting millions of people. Probiotics and postbiotics are associated with valuable compounds with antibacterial, anti-inflammatory, and immunomodulatory effects, preserving renal function in CKD patients. The current study is aimed to evaluate the efficacy of Limosilactobacillus fermentum (L. fermentum) and its postbiotic in an animal model of cisplatin-induced CKD. METHODS: The animals were divided into four experimental groups (normal mice, CKD mice with no treatment, CKD mice with probiotic treatment, and CKD mice with postbiotic treatment). CKD mice were induced by a single dose of cisplatin 10 mg/kg, intraperitoneally. For 28 days, the cultured probiotic bacteria and its supernatant (postbiotic) were delivered freshly to the related groups through their daily water. Then, blood urea nitrogen (BUN) and creatinine (Cr) of plasma samples as well as glutathione (GSH), lipid peroxidation, reactive oxygen species, and total antioxidant capacity of kidneys were assessed in the experimental mice groups. In addition, histopathological studies were performed on the kidneys. RESULTS: Application of L. fermentum probiotic, and especially postbiotics, significantly decreased BUN and Cr (P < 0.0001) as well as ROS formation and lipid peroxidation levels (P < 0.0001) along with increased total antioxidant capacity and GSH levels (P < 0.001). The histopathologic images also confirmed their renal protection effect. Interestingly, the postbiotic displayed more effectiveness than the probiotic in some assays. The improvement effect on renal function in the current model is mainly mediated by oxidative stress markers in the renal tissue. CONCLUSIONS: In conclusion, it was found that the administration of L. fermentum probiotic, and particularly its postbiotic in cisplatin-induced CKD mice, showed promising effects and could successfully improve renal function in the animal model of CKD. Therefore, probiotics and postbiotics are considered as probably promising alternative supplements to be used for CKD.

Parasporin-4, a novel apoptosis inducer of breast cancer cells produced by Bacillus thuringiensis.

BACKGROUND: Parasporin (PS) proteins have cytocidal activity preferential for various human malignant cells. The purpose of this investigation was to see if the PS separated from B. thuringiensis strain E8 isolate had any particular cytotoxicity against breast cancer. METHODS AND RESULTS: The extracted spores-crystal proteins were solubilized and digested with proteinase K. Cytotoxicity effects were analysed by MTT assay. Caspases activities were measured using ELISA. SDS-PAGE analysis was performed for determination of molecular weight of Cry protein. Identification of extracted proteins function was evaluated by MALDI-TOF MS analysis. Breast cancer cells line (MCF-7) was highly susceptible to 1 mg/mL PS and showed apoptosis characteristics, but it has no effects on the normal cells (HEK293). Apoptosis evaluation showed that caspases 1, 3, 9 and BAX were remarkably up-regulated in cancer cells, indicating the intrinsic pathway activation in these cells. PS Size was determined using SDS-PAGE in E8 isolate as 34 kDa and a 25 kDa digested peptide was identified as PS4. The function of PS4 was reported as an ABC-transporter by spectrometry. CONCLUSION: The data of the present study show that PS4 is a selective cytotoxic protein against breast cancer and a molecule with a lot of potentials for next researches.

Age-, Sex-, and Puberty-Associated Reference Intervals for Lipid Profile in Iranian Children and Adolescents.

Childhood dyslipidemia is considered a major worldwide health issue. Identification of children with dyslipidemia is notably essential for healthcare providers in establishing and releasing recommendations for the management and prevention of future CVD. In the present study, we provided reference values for the lipid profile from Kawar (a city in the south of Iran) cohort of healthy children and adolescents aged 9-18 years. 472 subjects (234 girls and 238 boys) contributed to the current prospective cohort study using a systematic random sample stratified by age. Fasting lipid levels were measured by enzymatic reagents. Dual-energyX-ray absorptiometry (DEXA) was used to evaluate puberty based on the Tanner stages. LMS Chart Maker and Excel software were used to construct the gender-specific reference plots showing the 3, 10, 25, 50, 75, 90, and 97th percentiles of BMI, cholesterol, TG, HDL, TC, LDL, and non-HDL. The outcomes revealed that concentrations of TC, LDL, and non-HDL were drastically greater in girls as compared to boys. TG increased with age in both genders, while HDL, TC, LDL, and non-HDL declined. We also observed that puberty was associated with higher lipid values in boys and girls except for TG in boys. Our study prepared age- and sex-specific reference intervals for the lipid profile in Iranian children and adolescents. Converted to age and gender percentiles, these reference intervals are expected to serve as an effective and consistent tool for doctors to identify dyslipidemia among children and adolescents.

The ameliorative role of specific probiotic combinations on bone loss in the ovariectomized rat model.

BACKGROUND: Osteoporosis, a skeletal disease described by impaired bone strength, cause an increased risk of fractures. We aimed in this study to clarify which particular wise combination of probiotics has the most beneficial effect in the rat model of osteoporosis. METHODS: Sixty-three mature female Sprague Dawley rats (12-14 weeks old, weight 200 ± 20 g) were ovariectomized and then divided into nine random groups, each group consisting of 7 rats. Lactic acid bacteria were isolated from traditional fermented yogurt on the northern coast of the Persian Gulf. Seven combinations of probiotics, each containing three probiotic strains, were designed and administered (1 × 10 9 CFU / ml/strain daily along with their water) to treat ovariectomized rats. The period from ovariectomy to eutanásia was 3 months. For evaluating femur, spine, and tibia, bone mineral density (BMD), and bone mineral content (BMC), Dual-energy X-ray absorptiometry (DEXA) scans were performed. Also, effect of probiotic combinations was assessed on biochemical markers including vitamin D, calcium, phosphorus, and alkaline phosphatase in serum. RESULTS: Combination NO 4, containing L. acidophilus, B. longum, and L. reuteri, is the most influential group on global, spine, and femur BMD. Combination NO 3, containing L. acidophilus, L. casei, and L. reuteri, also significantly affects the BMD of the tibia among the treatment group. We found that the combination NO 4 had the most significant ameliorative effect on global BMC. Also, combination NO 1 (comprising L. acidophilus, L. casei, and B. longum), NO 6 (containing L. casei, B. longum, and Bacillus coagulans), NO 7 (containing L. casei, L. reuteri, and B. longum), and NO 4 had the most considerable raising effect on spine BMC. In addition, the serum calcium and Vitamin D concentration in the groups NO 4, 6, and 7 were significantly higher than in OVX groups, whereas the alkaline phosphatase concentration was considerably reduced in these groups. CONCLUSION: Among nine effective probiotics, a combination containing L. acidophilus, B. longum, and L. reuteri is the most influential group in ovariectomized osteoporotic rat.

Recent advances in antiviral effects of probiotics: potential mechanism study in prevention and treatment of SARS-CoV-2.

SARS-CoV-2 is responsible for coronavirus disease 2019 (COVID-19), progressively extended worldwide countries on an epidemic scale. Along with all the drug treatments suggested to date, currently, there are no approved management protocols and treatment regimens for SARS-CoV-2. The unavailability of optimal medication and effective vaccines against SARS-CoV-2 indicates the requirement for alternative therapies. Probiotics are living organisms that deliberate beneficial effects on the host when used sufficiently and in adequate amounts, and fermented food is their rich source. Probiotics affect viruses by antiviral mechanisms and reduce diarrhea and respiratory tract infection. At this point, we comprehensively evaluated the antiviral effects of probiotics and their mechanism with a particular focus on SARS-CoV-2. In this review, we suggested the conceptual and potential mechanisms of probiotics by which they could exhibit antiviral properties against SARS-CoV-2, according to the previous evidence concerning the mechanism of antiviral effects of probiotics. This study reviewed recent studies that speculate about the role of probiotics in the prevention of the SARS-CoV-2-induced cytokine storm through the mechanisms such as induction of anti-inflammatory cytokines (IL-10), downregulation of pro-inflammatory cytokines (TNF-α, IL-2, IL-6), inhibition of JAK signaling pathway, and act as HDAC inhibitor. Also, the recent clinical trials and their outcome have been reviewed. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-022-01147-y.

Effect of 8% arginine toothpaste on Streptococcus mutans in patients undergoing fixed orthodontic treatment: randomized controlled trial.

OBJECTIVE: To assess the effect of toothpaste containing 8% arginine on Streptococcus mutans (S. mutans) in dental plaque around orthodontic brackets, and to draw a comparison with a regular fluoride toothpaste. TRIAL DESIGN: A single-center, parallel-arm, triple-blind, randomized controlled trial was conducted. METHODS: The clinical trial was conducted at the Orthodontic Clinic, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Seventy-two patients (age range: 15-30 years) who required fixed orthodontic treatment were recruited and randomly assigned to arginine and fluoride groups. Randomization was performed using RANDOM.ORG online software, and the participants were divided into two parallel groups, with a 1:1 allocation ratio. Patients were requested to brush their teeth twice daily for 30 days with an experimental toothpaste. Plaque sampling was performed at two intervals, namely at the beginning of the study (T0) and 30 days later (T1). Real-time PCR was used to assess plaque samples in terms of the number of S. mutans surrounding stainless steel brackets in orthodontic patients. A triple-blind design was employed. RESULTS: The baseline characteristics (age, sex, and the relative number of S. mutans) between the groups were similar (p>0.05). Only the arginine group showed a significant decrease in the relative number of bacteria between T0 and T1 (p=0.02). CONCLUSION: Arginine is an important prebiotic agent in maintaining healthy oral biofilms, and prevent dental caries during fixed orthodontic treatments. TRIAL REGISTRATION: The trial was registered at the Iranian Registry of Clinical Trials (IRCT20181121041713N2), https://en.irct.ir/user/trial/42409/view.

Importance of TP53 codon 72 and intron 3 duplication 16 bp polymorphisms and their haplotypes in susceptibility to sarcopenia in Iranian older adults.

BACKGROUND: Sarcopenia is described as age-related progressive skeletal muscle failure that results in marked reduction in the patient's independence and life quality. In this study, we explored the association of TP53 exon 4 Arg72pro (rs1042522) and Intron 3 16-bp Del/Ins (rs17878362) polymorphisms and their haplotypes with sarcopenia, anthropometric, body composition and biochemical parameters. METHODS: A total of 254 older individuals (65 sarcopenic and 189 healthy) were recruited in this research and genotyped by PCR-RFLP. Linear regression was applied to find the correlation between TP53 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 polymorphism and haplotypes and the risk of sarcopenia was investigated by logistic regression. RESULTS: Arg/Pro genotype carriers was at a lower (ORadj = 0.175, 95% CI = 0.068 - 0.447; P < 0.001) risk of sarcopenia compared to the Arg/Arg group. In haplotypes analysis, Arg-Ins (ORadj: 0.484, 95% CI = 0.231 - 1.011, P = 0.043) and Pro-Ins (ORadj: 0.473, 95% CI = 0.210 - 1.068, P = 0.022) haplotypes showed decreased risk of developing sarcopenia. Moreover, in the case of codon 72 polymorphism, skeletal muscle mass, appendicular lean mass (ALM), skeletal muscle mass index (SMI), hand grip strength and Triglycerides, for Intron 3 16-bp Del/Ins polymorphism, albumin, calcium, cholesterol, and LDL were different, and for the haplotypes, skeletal muscle mass, SMI, ALM, HDL and triglycerides were significantly different between groups. CONCLUSIONS: We suggested that the Arg/Pro genotype of the codon 72 polymorphism in exon 4 of TP53, and Arginine-Insertion and Proline-Insertion haplotypes might decrease the risk of sarcopenia in Iranian older adults.

The impact of GSTM1 and GSTT1 polymorphisms on susceptibility to gestational diabetes in Iranian population.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized as a common metabolic disorder during pregnancy which is associated with glucose intolerance and insulin resistance. Genetic predisposition could contribute to the development of GDM. METHODS: We conducted a case-control study to inspect the impact of GSTM1 and GSTT1 polymorphism on GDM susceptibility in Iranian population. The population consisted of 149 pregnant women with GDM as cases, and 138 healthy pregnant women without any history of GDM as controls. Polymerase chain reaction-restriction fragment length polymorphism method was applied to determine the GSTM1 and GSTT1 gene polymorphisms. RESULTS: There were statistically significant differences between the cases and controls in terms of age (p = .005), BMI (p < .001), family history of gestational diabetes (p < .001), FBS (p = .001), TG (p ≤ .001), and HDL (p = .003). However, no significant differences were observed in TC (p = .078) and LDL (p = .062). There were significant differences between GSTM1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 2.3 (1.4-3.7), p < .001]. The distribution of GSTM1-null genotype was found to be significantly higher in GDM patients (68.6%) than the control group (48.5%). No significant variance was detected between GSTT1 polymorphism (Null and present) in the case and controls groups [OR (95% CI); 1.1 (0.6-1.6), p = .088]. The frequency of GSTM1 null/GSTT1 null [OR (95% CI); 2.7 (1.2-5.2), p = .01] and GSTM1 null/GSTT1 present [OR (95% CI); 2.6 (1.4-4.8), p = .002] genotypes significantly differed between the GDM and control groups. CONCLUSION: It seems that GSTM1 null genotype might be considered as GDM risk factor in Iranian population.

Effect of 8% arginine toothpaste on Streptococcus mutans in patients undergoing fixed orthodontic treatment: randomized controlled trial

ABSTRACT Objective: To assess the effect of toothpaste containing 8% arginine on Streptococcus mutans (S. mutans) in dental plaque around orthodontic brackets, and to draw a comparison with a regular fluoride toothpaste. Trial design: A single-center, parallel-arm, triple-blind, randomized controlled trial was conducted. Methods: The clinical trial was conducted at the Orthodontic Clinic, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Seventy-two patients (age range: 15-30 years) who required fixed orthodontic treatment were recruited and randomly assigned to arginine and fluoride groups. Randomization was performed using RANDOM.ORG online software, and the participants were divided into two parallel groups, with a 1:1 allocation ratio. Patients were requested to brush their teeth twice daily for 30 days with an experimental toothpaste. Plaque sampling was performed at two intervals, namely at the beginning of the study (T0) and 30 days later (T1). Real-time PCR was used to assess plaque samples in terms of the number of S. mutans surrounding stainless steel brackets in orthodontic patients. A triple-blind design was employed. Results: The baseline characteristics (age, sex, and the relative number of S. mutans) between the groups were similar (p>0.05). Only the arginine group showed a significant decrease in the relative number of bacteria between T0 and T1 (p=0.02). Conclusion: Arginine is an important prebiotic agent in maintaining healthy oral biofilms, and prevent dental caries during fixed orthodontic treatments. Trial registration: The trial was registered at the Iranian Registry of Clinical Trials (IRCT20181121041713N2), https://en.irct.ir/user/trial/42409/view.

RESUMO Objetivo: Avaliar o efeito de um dentifrício contendo arginina a 8% no Streptococcus mutans (S. mutans) da placa bacteriana ao redor de braquetes ortodônticos, e compará-lo a um dentifrício fluoretado convencional. Desenho do estudo: Foi conduzido um estudo unicêntrico, com braços paralelos, triplo-cego, controlado e randomizado. Métodos: O ensaio clínico foi conduzido na Clínica de Ortodontia da Faculdade de Odontologia da Universidade de Ciências Médicas de Shiraz, no Irã. Setenta e dois pacientes (com idades variando de 15 a 30 anos) que necessitavam de tratamento ortodôntico com aparelho fixo foram recrutados e alocados aleatoriamente nos grupos arginina ou flúor. A randomização foi feita usando o programa on-line RANDOM.ORG, e os participantes foram divididos em dois grupos paralelos, com proporção de alocação de 1:1. Solicitou-se aos pacientes que escovassem os dentes duas vezes ao dia com a pasta experimental, durante 30 dias. Amostras da placa bacteriana foram coletadas em dois intervalos: ao começo do estudo (T0) e após 30 dias (T1). Um PCR em tempo real foi usado para avaliar as amostras de placa, em termos de números de S. mutans ao redor dos braquetes de aço inoxidável nos pacientes ortodônticos. Um desenho de estudo triplo-cego foi usado. Resultados: As características iniciais (idade, sexo e quantidade relativa de S. mutans) foram semelhantes entre os grupos (p>0,05). Apenas o grupo arginina mostrou uma redução significativa na quantidade de bactérias entre T0 e T1 (p=0,02). Conclusão: A arginina é um agente prebiótico importante na manutenção de biofilmes bucais saudáveis, e previne as cáries dentárias durante o tratamento ortodôntico com aparelho fixo. Registro do ensaio: O ensaio foi registrado no Iranian Registry of Clinical Trials (IRCT20181121041713N2), https://en.irct.ir/user/trial/42409/view.

The Beneficial Effects of Probiotics via Autophagy: A Systematic Review.

Probiotics are living microorganisms increasingly used to treat or modulate different diseases or disorders because of their benefits and also low adverse reaction, and their positive and protective effects on various cells and tissues have been reported. The mechanisms by which probiotics exert their beneficial effects in different cells and tissues were investigated, and autophagy is one of the main mechanisms to induce their positive effects. Autophagy is a conserved process that occurs in all eukaryotic cells and plays an essential role in homeostasis and cell survival by degrading damaged and dysfunctional intracellular organelles. On the other hand, the role of autophagy is diverse in different tissues and situations, and cell death derived from autophagy has been observed in some cells. This search was done in PubMed, WOS, and Scopus using the keywords probiotic, microbiota, and autophagy. The search strategy was focused on the in vitro and animal model studies, and the included filters were English language publications and full-text articles (by June 2020). Studies that investigated other underlying mechanisms except autophagy were excluded. Among more than 105 papers, 24 studies were considered eligible for more evaluation. The obtained results indicated that most studies were performed on intestinal cell lines or tissue compared with other types of cell lines and tissue. This review article discusses our current understanding of the probiotic effects through autophagy in different cell lines and tissues that would be a useful guide to daily and clinical usage of these living microorganisms, but despite promising results of this systematic review, further studies need to assess this issue. This systematic review has demonstrated that autophagy is an effective mechanism in inducing beneficial effects of probiotics in different tissues.

Exploring the bone sparing effects of postbiotics in the post-menopausal rat model.

BACKGROUND: Post-menopausal osteoporosis is a concern of health organizations, and current treatments do not seem enough. Postbiotics as bioactive compounds produced by probiotics may be an attractive alternative for bone health. In this study, we prepared, formulated, and compared the effects of cell lysate and supernatant of five native probiotic strains (Lactobacillus acidophilus, Lactobacillus reuteri, Lactobacillus casei, Bifidobacterium longum, and Bacillus coagulans) in ovariectomized (OVX) rats. METHODS: The probiotic strains were isolated, and their cell-free supernatants and biomasses as postbiotics were extracted and formulated using standard microbial processes. The Sprague-Dawley rats were fed by 1 × 109 CFU/ml/day postbiotic preparations for 4 weeks immediately after ovariectomy. Dual-energy X-ray absorptiometry (DEXA) scans were accomplished to evaluate femur, spine, and tibia BMD. The serum biochemical markers [calcium, phosphorus, and alkaline phosphatase] were assessed. RESULTS: Postbiotics could considerably improve the global and femur area in OVX rats. In the case of global bone mineral density (BMD), Lactobacillus casei lysate and supernatant, Bacillus coagulans lysate and supernatant, lysate of Bifidobacterium longum and Lactobacillus acidophilus, and Lactobacillus reuteri supernatant significantly increased BMD. We found Bacillus coagulans supernatant meaningfully enriched tibia BMD. CONCLUSION: Postbiotic could ameliorate bone loss resulting from estrogen deficiency. Also, the effects of postbiotics on different bone sites are strain-dependent. More clinical studies need to explore the optimal administrative dose and duration of the specific postbiotics in protecting bone loss.

The association between TP53 rs1625895 polymorphism and the risk of sarcopenic obesity in Iranian older adults: a case-control study.

BACKGROUND: Aging and obesity are the two major global health concerns. Sarcopenia, an age-linked disease, wherein a progressive loss of muscle volume, muscle strength, and physical activity occurs. In this study we evaluated the association of TP53 rs1625895 polymorphism with the susceptibility to sarcopenic obesity in Iranian old-age subjects. METHODS: Total of 176 old individuals (45 sarcopenic and 131 healthy) were recruited in this research and genotyped by PCR-RFLP. BMI, Skeletal Muscle Mass Index, body composition, Handgrip Strength, Gait Speed (GS), and biochemical parameters were measured. Chi-square test was done for genotypes and alleles frequency. Linear regression was applied to find the correlation between TP53 rs1625895 polymorphism, and biochemical and anthropometric parameters. The correlation between TP53 rs1625895 and the risk of sarcopenia and sarcopenic obesity was investigated by logistic regression. RESULTS: G allele was significantly higher in sarcopenic obesity group [P = 0.037, OR (CI 95%) = 1.9 (1.03-3.5)] compared to A allele. BMI (P = 0.049) and LDL (P = 0.04) were significantly differed between genotypes when GG was compared to AA/AG genotype. The results revealed when GG genotype compared to AA/AG genotype in adjusted model for age, the risk of sarcopenic obesity [P value = 0.011, OR (CI 95%); 2.72 (1.25-5.91)] increased. Similarly, GG/AG genotype increased the risk of sarcopenic obesity [P value = 0.028, OR (CI 95%); 2.43 (1.10-5.36)] in adjusted model for age compared to AA genotype. CONCLUSIONS: We suggested that TP53 rs1625895 polymorphism may increase the risk of sarcopenic obesity in Iranian population.

Anti-androgenic effect of astaxanthin in LNCaP cells is mediated through the aryl hydrocarbon-androgen receptors cross talk.

The aim of this study was to investigate the anti-androgenic effects of astaxanthin (AST) on human prostatic cancer cell growth, and its impact on androgen receptor (AR) signaling using prostate cancer (PCa) cell line LNCaP. LNCaP cells were treated with AST alone and in combination with CH223191 and flutamide (Flu) in the presence and absence of testosterone. MTT assay, cellular prostate-specific antigen (PSA) and dihydrotestosterone (DHT) production, mRNA levels of CYP1A1, PSA, Kallikrein-Related Peptidase 2 (KLK2), Transmembrane Serine Protease 2 (TMPRSS2), and AR genes were measured as endpoints. The expression of CYP1A1, PSA, KLK2, TMPRSS2, and AR mRNA levels was decreased which results in reducing the production of PSA and DHT in the presence of testosterone. Our data clearly demonstrate that AST has a potential ability to suppress the human prostate LNCaP cells growth at high concentrations. AST was able to repress the testosterone-induced transcription of AR-target genes. PRACTICAL APPLICATIONS: Astaxanthin is a natural compound with the most potent antioxidant activity among other antioxidants. In the current study, ASX suppressed the LNCaP cells at high concentrations. Furthermore, AST inhibited testosterone-induced transcriptional activation of androgen-related genes. AST induced the expression of CYP1A1, which is able to metabolize the steroid hormones. It seems that AST can act as AhR exogenous ligand by induction of CYP1A1, which results in testosterone metabolism and consequent suppression of AR genes. So that, AST could prevent the growth of testosterone-dependent PCa cells, downregulate downstream genes in testosterone pathways, and enhance the metabolism of testosterone via AhR pathway. Collectively, AST could be considered as a potential candidate for the treatment of PCa.

Protective effect of the olive hydroalcoholic extract on estrogen deficiency-induced bone loss in rats in comparison with estradiol.

OBJECTIVE: Osteoporosis, as a skeletal disorder caused by aging, is considered a major health problem. This work was planned to assess the effect of the black olive hydroalcoholic extract on bone mineral density and biochemical parameters in ovariectomized rats. MATERIALS AND METHODS: Ninety 6-month-old female Sprague Dawley rats were randomly assigned into 7 sets: control (received saline); sham-operated control, Ovariectomized (OVX) rats (received saline); 3 groups of black olive-supplemented OVX rats (respectively, receiving 250, 500, and 750 mg/kg body wt black olive extract orally); and estrogen group (receiving 3 mg/kg/day estradiol valerate). Blood samples were collected 2, 4 and 6 months after treatment to measure calcium (Ca), alkaline phosphatase (ALP), and phosphorus (P). Dual-energy X-ray absorptiometry (DEXA) was applied to measure the bone mineral density (BMD). Global, lumbar spine and lower limb BMD was measured. RESULTS: Ca concentration was significantly increased in the group treated with the highest dose of black olive hydroalcoholic compared to the OVX group (P<0.001). In addition, a significant decrease in ALP concentrations in the group treated with the highest dose of black olive hydroalcoholic comparing with the OVX group was observed (P<0.001). The global, tibia, femur and spine BMD in the group treated with the highest dose of black olive hydroalcoholic and estrogen group were significantly increased compared to the OVX group (P<0.05). CONCLUSION: Black olive hydroalcoholic extract at the dose of 750 mg/kg, prevented bone loss and augmented bone mineral density and could be a possible candidate for the management of osteoporosis.

The rs2302685 polymorphism in the LRP6 gene is associated with bone mineral density and body composition in Iranian children.

BACKGROUND: Some 60-80% of the variability in bone mineral density (BMD) is determined by genetic factors. In the present study, we investigated the impact of the rs2302685 polymorphism of LRP6 on BMD and body composition in Iranian children. METHODS: In total, 200 children (101 boys and 99 girls) were enrolled in the study. Body composition and BMD were computed using the Hologic DXA System (Hologic, Marlborough, MA, USA). The single nucleotide polymorphism of LRP6 rs2302685 (V1062I) was determined using a polymerase chain reaction/restriction fragment length polymorphism. A generalized linear model was performed to find the association between LRP6 polymorphisms, BMD and body composition in two adjusted models. RESULTS: In model 1, a significant difference was found between LRP6 (rs2302685) polymorphism, trochanteric BMD (p = 0.007), intertrochanteric BMD (p = 0.007), total fat (p = 0.001), total fat (%) (p = 0.034), total lean mass (p = 0.031), total Lean + BMC (p = 0.036) and total mass (p = 0.001). In model 2, LRP6 (rs2302685) polymorphisms showed a significant effect on the trochanteric BMD (p = 0.005), intertrochanteric BMD (p = 0.005), total fat (p = 0.001), total fat (%) (p = 0.013) and total mass (p = 0.01). Total fat, total fat (%) and total body mass were higher in subjects with the CC genotype compared to the TT/CT genotype, whereas total lean mass and total Lean + BMC were higher in the TT/CT genotype. CONCLUSIONS: The present study shows that the LRP6 polymorphism may be associated with body composition and BMD in Iranian children.

Anti-androgenic effect of 6-formylindolo[3,2-b]carbazole (FICZ) in LNCaP cells is mediated by the aryl hydrocarbon-androgen receptors cross-talk.

The factual impact of endogenously activated AHR by 6-formylindolo[3,2-b]carbazole (FICZ), an endogenous ligand of AHR on androgen receptor (AR) was aim of this study. In this study, LNCaP cells were exposed to FICZ, CH223191 and flutamide (Flu) alone or in combination in the presence and absence of testosterone. CYP1A1 enzyme activity, cell viability, cellular prostate-specific antigen (PSA) and dihydrotestosterone (DHT) production, mRNA levels of PSA, KLK2, TMPRSS2, and AR genes were measured as endpoints. A declining in the expression of androgen- responsive target genes was seen by either Flu or FICZ in the presence of testosterone. Furthermore, the forced decrease in the expression of AR target genes resulted in 41% and 31% decline in the DHT and PSA concentrations respectively. Taken together, endogenously activated AHR plays a regulatory role on AR. Therefore, FICZ might be an effective chemical in treating prostate cancer.