The Association Between CYP2R1 rs10741657 Polymorphisms and Bone Variables, Vitamin D, and Calcium in Iranian Children and Adolescents: A Cross-Sectional Study.

Osteoporosis is a common disorder with a strong genetic component. Bone mineral density (BMD), vitamin D, and calcium levels declining are a main contributor of osteoporosis and fragility fractures. This cross-sectional study designed to explore the possible link between CYP2R1 rs10741657 polymorphism and BMD of the total hip, lumbar spine and femoral neck, vitamin D, and calcium in Iranian children and adolescents. 247 children and adolescents (127 girls and 120 boys) between 9 and 18 years old from Kawar (an urban area located 50 km east of Shiraz, the capital city of the Fars province in the south of Iran) were randomly selected based on age-stratified systematic sampling and recruited for genetic analysis. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping CYP2R1 rs10741657. Anthropometric, biochemical, and bone mineral density (BMD) parameters were also measured. The results specified that in the dominant [P < 0.0001, - 2.943 (- 4.357-1.529)] and over-dominant [P < 0.0001, 2.789 (1.369-4.209)] models, vitamin D concentration significantly differed between genotypes. The highest vitamin D levels were displayed for participants carrying the rs10741657 AG genotype (16.47 ng/ml). In regard to calcium, in a dominant model [P = 0.012, 0.194 (0.043-0.345)] and over-dominant model [P = 0.008, 0.206 (- 0.357-0.055), there was a significant association. AG genotype displayed the highest (9.96 mg/dl) and GG genotype the lowest (9.75 mg/dl) calcium values. This study reported the association of CYP2R1 rs10741657 polymorphisms with calcium and vitamin D levels in Iranian children and adolescents.

FRAX-derived intervention and assessment thresholds for osteoporosis in ten Middle Eastern countries.

This study established FRAX-based age-specific assessment and intervention thresholds for ten Middle Eastern countries where FRAX is currently available, but the lack of specific thresholds has limited its usefulness. The intervention thresholds ranged from 0.6 (Saudi Arabia) to 36.0% (Syria) at the ages of 40 and 90 years, respectively. INTRODUCTION: Developing fracture risk assessment tools allows physicians to select patients for therapy based on their absolute fracture risk instead of relying solely on bone mineral density (BMD). The most widely used tool is FRAX, currently available in ten Middle Eastern countries. This study aimed to set FRAX-derived assessment and intervention thresholds for individuals aged 40 or above in ten Middle Eastern countries. METHODS: The age-specific 10-year probabilities of a major osteoporotic fracture (MOF) for a woman with a BMI of 25.0 kg/m2, without BMD and clinical risk factors except for prior fracture, were calculated as intervention Threshold (IT). The upper and lower assessment thresholds were set at 1.2 times the IT and an age-specific 10-year probability of a MOF in a woman with a BMI of 25.0 kg/m2, without BMD, prior fracture, and other clinical risk factors, respectively. IT is utilized to determine treatment or reassurance when BMD facilities are unavailable. However, with BMD facilities, assessment thresholds can offer treatment, reassurance, or bone densitometry based on MOF probability. RESULTS: The age-specific IT varied from 0.9 to 11.0% in Abu Dhabi, 2.9 to 10% in Egypt, 2.7 to 14.0% in Iran, 1.0 to 28.0% in Jordan, 2.7 to 27.0% in Kuwait, 0.9 to 35.0% in Lebanon, 1.0 to 16.0% in Palestine, 4.1 to 14% in Qatar, 0.6 to 3.7% in Saudi Arabia, and 0.9 to 36.0% in Syria at the age of 40 and 90 years, respectively. CONCLUSIONS: FRAX-based IT in Middle Eastern countries provides an opportunity to identify individuals with high fracture risk.

The association between healthy beverage index and sarcopenia in Iranian older adults: a case-control study.

BACKGROUND: Sarcopenia is a progressive disease with age-related loss of skeletal muscle mass, strength, and function. No study has investigated the association between healthy beverage index (HBI) and sarcopenia in older adults. Therefore, the present study aimed to investigate the association between HBI and sarcopenia in Iranian older adults. METHODS: In the present case-control study, 80 sarcopenic and 80 non-sarcopenic participants matched in sex were included. Body composition was measured using bioelectrical impedance analysis. Handgrip strength (HGS), skeletal muscle mass index (SMI), and gait speed were utilized to confirm sarcopenia. Also, a food frequency questionnaire was used to evaluate food intake. HBI score was calculated based on ten sub-components of the total beverages. Moreover, logistic regression was applied to assess the association between HBI and sarcopenia. RESULTS: In the crude model, we observed no significant association between HBI and the odds of sarcopenia. Still, after adjusting the confounders, the odds of developing sarcopenia decreased significantly in the second and last tertiles (T) (T2- odds ratio (OR) = 0.04, 95% confidence interval (CI): 0.01-0.25 and T3- OR = 0.10, 95% CI: 0.01-0.60). CONCLUSIONS: Our findings indicated that HBI is inversely related to the chance of sarcopenia. Therefore, to reduce the odds of sarcopenia, it is recommended to consume healthy drinks such as fruit juices and milk.

Association between oxidative balance score and sarcopenia in older adults.

Sarcopenia is a progressive skeletal muscle disease in which oxidative stress has been proposed as one of the primary markers. The oxidative balance score (OBS) represents the oxidative balance of a person's dietary pattern using the merged intake of anti-oxidants and pro-oxidants. Therefore, the present study assessed the association between OBS and sarcopenia in Iranian older adults. In the current study, 80 people with sarcopenia and 80 without it were considered the case and control groups, respectively. All controls were matched by sex with cases. To confirm sarcopenia, skeletal muscle mass index (SMI), handgrip strength (HGS) measurement, and gait speed were used. Also, body composition was measured by bioelectrical impedance analysis (BIA). A valid and reliable food frequency questionnaire (FFQ) was used to assess all participants' dietary intake of pro-oxidants and anti-oxidants. Conditional logistic regression was applied to assess the association between OBS and sarcopenia. In the bivariate model, we observed lower odds of sarcopenia in the second and last tertile of OBS in comparison to the first tertile (T) (T2 - odds ratio (OR) = 0.414, 95% confidence interval (CI) : 0.186-0.918 and T3 - OR = 0.101, 95% CI: 0.041-0.248). After adjusting for potential confounders, the association was not significant in second and last tertile of OBS in comparision to the first one. The present study's findings demonstrated that overcoming exposure to anti-oxidants over pro-oxidants, as illustrated by a higher OBS, is not related to lower odds of sarcopenia in older adults.

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 effect of zoledronic acid on hip geometry in renal transplant recipients: a double-blind placebo-controlled randomized study.

BACKGROUND: In renal transplant patients, bisphosphonates may prevent bone loss, but little is known about their effects on bone microarchitecture and geometrical hip parameters, as the key factors of bone stability. This study aimed to analyze the effect of zoledronic acid on the mentioned parameters in kidney transplant patients. METHODS: In this double-blind, randomized trial, 33 patients were followed for six months after administering either 4mg of zoledronic acid or a placebo. Bone mineral density (BMD) measurement of the spine, hip, radius, and whole body was obtained, and trabecular bone score (TBS) was evaluated using the software. Geometric assessment at the proximal femur was performed by the HSA program. RESULTS: Eighteen patients in the intervention group and 15 in the control group completed the study. The mean percentages of the changes in the BMD at the lumbar spine and whole body were significantly different between the placebo and intervention groups (-0.23% vs. 4.91% and -2.03% vs. 1.23%) (P < 0.05). Zoledronic acid appeared to enhance the subperiosteal diameter, endocortical diameter, and cross-sectional moment of inertia (CSMI) at the narrow neck in comparison with placebo (P < 0.05); however, no difference in TBS was observed between both groups (P > 0.05). CONCLUSIONS: We concluded that a single administration of zoledronic acid might ameliorate bone loss at the lumbar spine and the whole body and maintain the subperiosteal diameter, endocortical diameter, and CSMI as parameters of bone strength at the narrow neck of the proximal femur after six months in renal-transplant recipients. TRIAL REGISTRATION: This study was registered in IRCT (ID: IRCT20181202041821N1) on 04-05-2019.

Simultaneous adrenal and retroperitoneal myelolipoma resected by laparoscopic surgery: a challenging case.

BACKGROUND: Myelolipoma is a benign neoplasm of the adrenal cortex, composed of fat and hematopoietic cells. Although myelolipoma is benign, differentiation from adrenocortical cancer may be difficult. The presence of adrenal and extra-adrenal myelolipomas simultaneously is sporadic, making it a challenging case, especially when the preoperative diagnosis is ambiguous. CASE PRESENTATION: A 65-year-old man was referred to our clinic due to a mass in the adrenal fossa. In the abdominopelvic computed tomography (CT), a well-circumscribed fat-containing 78 × 61 × 65 mm bi-lobulated mass was reported in the left adrenal fossa. The first differential diagnosis was myelolipoma. The patient was then referred to our clinic for a mass excision. He was asymptomatic and was scheduled to undergo laparoscopic-assisted adrenalectomy. After adrenalectomy and mass dissection, surprisingly, another mass was detected in the retroperitoneal area. The second mass was also dissected. The final diagnosis was myelolipoma for both masses. The patient has been symptom-free for nine months after the operation. CONCLUSION: Simultaneous adrenal and extra-adrenal myelolipoma should be considered as one of the differential diagnoses. However, because this situation is extremely rare, the probability of malignancy should be highly regarded, and we suggest an obsessive approach when approaching this condition. It is essential to manage these cases on a case-by-case basis and tailor the management concerning intraoperative biopsy, the intraoperative appearance of tumors, and the location of extra-adrenal masses.

Hip structural analysis, trabecular bone score, and bone mineral density in post-menopausal women with type-2 diabetes mellitus: a multi-center cross-sectional study in the south of Iran.

This study aimed to evaluate bone mineral density (BMD), trabecular microarchitecture, and proximal hip geometry in diabetic postmenopausal women, where BMD alone cannot reflect bone strength adequately. We found significantly lower trabecular bone score and BMD at the distal radius and total forearm in diabetic subjects compared to controls. PURPOSE: The limitations resulting from the exclusive assessment of bone mineral density (BMD) in people with diabetes can lead to underestimation of microarchitectural and geometric changes, both of which play an essential role in the fracture risk. Therefore, we aimed to evaluate BMD, trabecular bone score (TBS), and hip structural analysis (HSA) in diabetic type-2 post-menopausal women and compare them with healthy postmenopausal subjects. METHODS: BMD was assessed at the lumbar spine, femoral sites, distal radius, and total forearm using dual-energy X-ray absorptiometry (DXA); TBS was measured based on DXA images using the software at the same region of interest as the BMD measurements; geometric assessment at the proximal femur was performed by the HSA program. RESULTS: A total of 348 ambulatory type-2 diabetic postmenopausal women and 539 healthy postmenopausal women were enrolled. TBS and BMD at the distal radius and total forearm were significantly (P value < 0.05) lower in cases compared to controls after age and body mass index (BMI) adjustment. In addition, degraded bone microarchitecture was significantly (P value < 0.05) more prevalent in diabetic subjects than in non-diabetic controls after adjusting for age and BMI. A number of geometric indices of the proximal hip were significantly lower in the controls than in those with diabetes (P-value < 0.05). CONCLUSION: This study may highlight the utility of the TBS and BMD at the distal radius and total forearm in subjects with type-2 diabetes mellitus, where the BMD at central sites may not adequately predict fracture risk.

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.

Osteoprotective effects of kefir fortified with omega-3 and vitamin C in ovariectomized rats.

Nutritional interventions can be valuable for the prevention of postmenopausal osteoporosis. This study aimed to investigate the effects of kefir fortified with omega-3 and vitamin C on the bone and uterus parameters of ovariectomized rats. Seventy-seven female Sprague-Dawley rats were ovariectomized or sham-operated. The ovariectomized rats were assigned to six groups and received 1 ml/day of distilled water (OVX group), milk, kefir, kefir fortified with omega-3 fatty acids (kefir+ω3), kefir fortified with vitamin C (kefir+vit-C) or kefir fortified with omega-3 and vitamin C (kefir+ω3+vit-C) for 12 weeks. The sham group also received 1ml/day of distilled water. Subsequently, bone mineral content (BMC) and bone mineral density (BMD) of various bones were assessed. Femurs and uteri were harvested for bone ash analysis and histopathological examinations, respectively. Sera were analyzed for carboxy-terminal cross-linked telopeptide of type 1 collagen, procollagen type 1 amino-terminal propeptide, calcium, phosphorous, tumor necrosis factor-α (TNF-α) and total antioxidant capacity levels. Ovariectomy resulted in significant reduction in bone density (P<0.05). Kefir+ω3+vit-C significantly improved BMC of lumbar spine (0.699±0.027 g compared with 0.580±0.018 in the OVX group), and kefir, kefir+vit-C and kefir+ω3+vit-C significantly increased BMD of tibia (0.118±0.003 g/cm2, 0.119±0.001 and 0.120±0.004 compared with 0.102±0.005 in the OVX group). Moreover, ovariectomy markedly elevated TNF-α level, which was significantly reversed by kefir+ω3+vit-C. Significant atrophy of the uterus was observed following ovariectomy, although the uterus parameters did not change by any of the interventions. In conclusion, kefir fortified with omega-3 fatty acids and vitamin C may have protective effects against bone loss through suppressing inflammation.

Validation of the Persian version of the sarcopenia-specific quality of life questionnaire (SarQoL®-IR).

BACKGROUND: The sarcopenia quality of life (SarQoL)® questionnaire is a specific tool to measure QoL in sarcopenia. The aim of this study was to validate the SarQoL® questionnaire for evaluation of sarcopenia-related quality of life in Iranian community-dwelling older adults. METHODS: Validity (discriminative power, construct validity), reliability (internal consistency, test-retest reliability), and floor/ceiling effects of SarQoL® questionnaire were evaluated in the current study. Moreover, the SarQoL® questionnaire was compared with the Short-Form 36-item (SF-36) and the EuroQoL 5-Dimensions (EQ-5D) questionnaires. RESULTS: Among 501 community-dwelling older adults, 128 elderly participants (including 88 sarcopenic individuals) were recruited for validation. Participants with sarcopenia had lower quality of life than non-sarcopenic individuals (Total Score: 39.37 ± 7.45 vs. 65.09 ± 7.85, p < 0.001). Also, the findings demonstrated a high internal consistency (Cronbach's alpha of 0.881), excellent test-retest reliability (ICC = 0.995, 95% CI 0.990-0.998), and no floor/ceiling effect of SarQoL® questionnaire. CONCLUSION: This is the first study to confirm the reliability and validity of the Persian version of the SarQoL® for the measurement of quality of life among Iranian sarcopenic older adults.

The Development and Validation of Elder Self-Neglect Scale (ESNS) in Iranian Community-dwelling Older Population.

The aim of this study was to develop a valid and reliable elder self-neglect scale (ESNS) for field research on Iranian community-dwelling older adults. This mixed-method exploratory study was conducted in three stages: (1) item generation using literature review, (2) item reduction by expert panels, and (3) assessing the psychometric properties. In the third stage, the face, content, and construct validity (exploratory factor analysis) were performed on the first sample (n = 450), and the final 26-item scale was developed. After that, confirmatory factor analysis and reliability were assessed on the second sample (n = 250). Data were analyzed using IBM-SPSS v.23 and AMOS v.24. Exploratory factor analysis identified six factors with a total variance of 77.53%. The goodness of fit was indicated by Structural Equation Modeling. The Cronbach's alpha was estimated at 0.85. The optimal cutoff point was 73. This scale with 26 items seems to be an effective tool in screening elder self-neglect.

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.

Association of thyroid function test abnormalities with preeclampsia: a systematic review and meta-analysis.

BACKGROUND: Preeclampsia is a life-threatening disorder during pregnancy and postpartum periods. Preeclampsia can affect the activity of many organs. It is very important because if this disorder is associated with changes in thyroid function, it can affect the results of maternal and fetal tests. Accordingly, the aim of this meta-analysis study was to assess the abnormalities in thyroid function tests in preeclampsia. METHODS: Studies were selected through a systematic search of the MEDLINE/PubMed, Scopus, Web of Science Core Collection, and Google Scholar databases in 31st August 2021. Also, reference lists of review articles and relevant studies were manual-searched to identify other potentially eligible studies. English studies that compared TSH, T4 and T3 of normal pregnant with preeclamptic women (Known to be normotensive before pregnancy; gestational age 20 week or more; singleton pregnancy; no previous history of thyroid dysfunction) were screened. Data sets were screened for eligibility by two independent reviewers. Articles were assessed by the Newcastle-Ottawa Scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for quality assessment of evidence on outcome levels. RESULTS: After reviewing 886 published studies, 63 observational studies were selected and used for this meta-analysis. The study population included 21,528 pregnant women. The findings revealed that TSH (SMD = 1.70, 95%CI: 1.39 to 2.02; p < 0.001) was significantly higher in preeclamptic women. TT4 (SMD = -0.82, 95%CI: -1.16, -0.49; p < 0.001), TT3 (SMD = -0.88, 95%CI: -1.36 to -0.41; p < 0.001) and FT3 (SMD = -0.59, 95%CI: -0.91 to -0.27; p < 0.001) were less in preeclamptic women. There was no statistically significant difference in FT4 between two groups (SMD = 0.002, 95%CI: -0.27 to 0.27; p = .990). The results of publication bias and sensitivity analysis confirmed the reliability and stability of this meta-analysis. The quality of evidence was regarded as moderate, low, and very low for these risk factors according to the GRADE approach. CONCLUSIONS: Findings of this meta-analysis indicated preeclamptic women were more at risk of changes in thyroid function tests. In order to prevent thyroid disorders, it is recommended that thyroid function tests be performed in women with pre-eclampsia.

Probabilistic prediction of segmental body composition in Iranian children and adolescents.

BACKGROUND: Adolescents' body composition is considered an important measure to evaluate health status. An examination of any of the segmental compartments by anthropometric indices is a more usable method than direct methods. OBJECTIVES: To propose a method based on the network approach for predicting segmental body composition components in adolescent boys and girls using anthropometric measurements. METHODS: A dual-energy X-ray absorptiometry (DXA) dataset in the south of Iran, including 476 adolescents (235 girls and 241 boys) with a range of 9-18 years, was obtained. Several anthropometric prediction models based on the network approach were fitted to the training dataset (TRD 80%) using bnlearn, an R add-in package. The best fitted models were applied to the validation dataset (VAD 20%) to assess the prediction accuracy. RESULTS: Present equations consisting of age, weight, height, body mass index (BMI), and hip circumference accounted for 0.85 (P < 0.001) of the variability of DXA values in the corresponding age groups of boys. Similarly, reasonable estimates of DXA values could be obtained from age, weight, height, and BMI in girls over 13 years, and from age, weight, height, BMI, and waist circumference in girls under 13 years, respectively, of 0.77 and 0.83 (P < 0.001). Correlations between robust Gaussian Bayesian network (RGBN) predictions and DXA measurements were highly significant, averaging 0.87 for boys and 0.82 for girls (P < 0.001). CONCLUSIONS: The results revealed that, based on the present study's predictive models, adolescents' body composition might be estimated by input anthropometric information. Given the flexibility and modeling of the present method to test different motivated hypotheses, its application to body compositional data is highly appealing.

Eugenol: A New Option in Combination Therapy with Sorafenib for the Treatment of Undifferentiated Thyroid Cancer.

Thyroid cancer (TC) is the most common endocrine malignancy. Thyroidectomy and radiotherapy are common treatment modalities for patients with undifferentiated TC (UTC), and sorafenib is usually recommended to prevent a recurrence. However, malignant cells may evade chemotherapy-induced apoptosis, and combination therapy was developed to achieve better outcomes. This study investigated whether eugenol in combination with sorafenib was more effective than either substance individually in triggering apoptosis in the UTC. The IC50 of sorafenib and eugenol was determined in a UTC cell line (8305C) by MTT assay, and their synergistic effect in combination therapy was investigated. Flow cytometry was used to evaluate the rate of apoptosis in treated cells. To confirm that cell death occurred through apoptosis, immunoblotting was used to determine the relative cleavage of caspase-8 and caspase-9. The IC50 of sorafenib was 20 µM, and that of eugenol was 2100 µM. The sorafenib-eugenol combination (1:105) showed synergistic effects at concentrations equal to or less than their IC50. The rate of apoptosis induction was higher in cells treated with eugenol or the eugenol-sorafenib combination compared to sorafenib-treated cells. The relative intensity of cleaved/un cleaved forms of caspase-8 increased in eugenol-treated cells compared to sorafenib-treated cells.Sorafenib and eugenol at concentrations equal to or less than their IC50 had a synergistic effect in 8305C cells. The most potent apoptotic effect was achieved with sorafenib and eugenol at their IC50. Lower doses of sorafenib could be used with eugenol to improve its efficacy while reducing its side effects.

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.

Preserving effect of Loboob (a traditional multi-herbal formulation) on sperm parameters of male rats with busulfan-induced subfertility.

OBJECTIVE: Male infertility secondary to exposure to gonadotoxic agents during reproductive age is a concerning issue. The aim of this experimental study was to determine the effect of Loboob on sperm parameters. METHODS: 55 healthy rats were selected, weighted and divided into five groups consisting of 11 rats each. The control group received no medication. Rats in Treatment Group 1 received 10mg/kg Busulfan and rats in Treatment Groups 2, 3, and 4 received 35,70 and 140 mg/kg Loboob respectively in addition to 10mg/kg Busulfan. Finally, the sperm parameters and weights of the rats were compared using the Kolmogorov-Smirnov, non-parametric Kruskal-Wallis, and Dunn-Bonferroni tests. RESULTS: All sperm parameters and weights were significantly decreased among rats receiving Busulfan. All dosages of Loboob were effective to enhance the motility of slow spermatozoa, while only in the rats given 70 and 140 mg/kg of Loboob saw improvements in progressively motile sperm percentages (0.024 and 0.01, respectively). Loboob at a dosage of 140mg/kg improved sperm viability. It did not improve normal morphology sperm or decrease immotile sperm counts. Loboob did not affect mean rat weight. CONCLUSIONS: Loboob offered a dose-dependent protective effect on several sperm parameters in rats with busulfan-induced subfertility.