Profiling several key milk miRNAs and analysing their signalling pathways in dairy sheep breeds during peak and late lactation.

BACKGROUND: The comprehensive understanding of microRNAs (miRNAs) in sheep milk during various lactation periods and their impact on milk yield and composition remains limited. OBJECTIVES: This study aimed to investigate the expression patterns of four highly expressed miRNAs in sheep milk and their association with milk composition and yield parameters during peak and late lactation stages. METHODS: A total of 40 healthy 4-year-old Akkaraman (n = 20) and Awassi (n = 20) ewes registered with the Ministry of Agriculture and Forestry of the Republic of Türkiye were used in the present study. For miRNA isolation from milk, the Qiagen miRNeasy Serum/Plasma Advanced Kit was utilised following the manufacturer's instructions. The expression levels of miRNAs were assessed using Qiagen miRNA PCR Assays. RESULTS: The significant fold changes in the expression levels of oar-miR-30a-5p, oar-miR-148a and oar-miR-181a were observed between peak and late lactation periods in the Awassi sheep breed. Conversely, only oar-miR-30a-5p and oar-miR-148a exhibited statistically significant changes in the Akkaraman sheep breed during the same lactation periods. Furthermore, oar-miR-21-5p demonstrated a significant fold change exclusively in peak lactation compared to Akkaraman and Awassi ewes. CONCLUSIONS: The findings suggest that the expression of the analysed miRNAs is influenced by both the lactation stage and different sheep breeds. This study offers valuable insights into the relationship between key miRNA expressions in sheep milk and milk composition and yield parameters during peak and late lactation, contributing to the existing knowledge in this field.

Lack of association between VNTR variant of the circadian gene (PER3) and major depressive disorder in a sample of a Turkish population.

Major depressive disorder (MDD), which is a prevalent psychiatric disorder, is characterized by sleep-wake disturbances. An underlying circadian rhythm disorder mainly may cause these disturbances. The study presented here was designed to investigate the existence of Period Circadian Regulator 3 (PER3) gene VNTR variant in MDD patients in Turkish population. A sample of 118 patients with MDD and 150 healthy volunteers were included in the study. The PER3 VNTR genotyping was performed on DNA by polymerase chain reaction (PCR) using specific primers. The prevalence rates of genotypes of 5/5, 5/4, and 4/4 profiles for the PER3 variant were 30.5%, 55.9%, and 13.6%, respectively, in patients with MDD, and 23.3%, 57.3%, and 19.3%, respectively in the control group. No significant difference was observed between the two groups in terms of either genotype distributions or allele frequencies of the VNTR variant of the PER3 gene (p > 0.05). There was no statistically significant association between the patients and the controls in terms of 5/5 + 4/5 versus 4/4 and 5/5 versus 4/5 + 4/4 (p > 0.05). The present results suggest that the PER3 VNTR variant was not associated with MDD in the Turkish population. However, further studies with other gene variants in different ethnic populations are needed to address the exact role of this variant in MDD.

The effect of RORA (RAR-Related Orphan Receptor Alpha) receptors on litter size in Akkaraman sheep breed.

In this study, the relationship between RORA 23bp indel genotype and allele frequency with twin pregnancy, fertility, live weight and milk yield in 106 female Akkaraman ewes raised in Elazig province was investigated. In the study conducted in Elâzig province, 10ml milk was collected from 106 Akkaraman sheep and DNA was extracted from these milk. In RORA 23bp indel genotype frequency, DD genotype was found more than ID and II genotypes and RORA 23bp indel in allele frequency, the D allele was found to be higher than the I allele. In both the first and second parity, the twinning rate was found to be lower. In both the first and second parity, the twinning rate was higher in the DD genotype, and it was observed that this genotype prominated middle livestock weight and milk yield. According to the results of our study, mutations in the RORA gene, which is a gene affecting reproductive efficiency in sheep, do not have a positive effect on fertility and twinning rate in Akkaraman sheep. To sum, this study provided theoretical references for the comprehensively research of the function of RORA gene and the breeding of Akkaraman Sheep. The 23-bp indel variants can be considered as molecular markers for litter size of sheep for marker-assisted selection breeding.

Oar-miR-16b and oar-miR-27a: negatively correlated with milk yield and milk protein in sheep.

The characterization of miRNAs from sheep milk and their effect on milk yield and composition in sheep are remain unclear. Therefore, the aim of this study was to determine the expression pattern of several important miRNAs, which are associated with lactation in the sheep milk between high and low lactating-yield ewe groups. In addition to experimentally obtained miRNA expression results, the miRNA target genes were determined by bioinformatics analysis to identify biological pathways involved. miRNAs found to differ significantly in the expression level between the groups were oar-miR-181a, oar-miR-23a, oar-miR-27a, oar-miR-16b and oar-miR-374. Also, oar-miR-27a was shown negative correlation with milk protein and lactose contents while oar-miR-16b was shown negative correlation with milk yield in the high milk yield group. The highest connected hub genes for miR-27a target genes were determined as MAPK14 and PPARG. Also, six genes (HSPA4L, DNAJA2, ATP6V1B2, PPP2R1A, PPP2R1B, and PRKAR2A) were detected as hub genes for miR-16b. In this study, the relationship between expression profiles of several important miRNAs in sheep milk and milk yield and milk composition were investigated for the first time in high and low lactating yield groups.

Acute treatment with dexketoprofen reduces penicillin induced epileptiform activity in wistar albino rats (dexketoprofen in penicillin induced seizure model).

AIM: Dexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats. METHOD: In this study, 28 male Wistar rats weighing 220-240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats' left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG). RESULTS: The low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05). CONCLUSION: This study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures.

The effect of dexketoprofen trometamol on WAG/Rij rats with absence epilepsy (dexketoprofen in absence epilepsy).

AIM: Epilepsy is one of the most common neurological diseases. Dexketoprofen (DEX) is a nonselective nonsteroidal anti-inflammatory drug that is used as an analgesic. The present study aimed to assess the efficiency of DEX on WAG/Rij rats by electrophysiologically and behaviorally. MATERIAL AND METHODS: Twenty-eight male WAG/Rij rats were used. The effects of acute treatment with DEX (5, 25, and 50 mg/kg, i.p) on absence-like seizures, and related psychiatric comorbidity were assessed. The ECoG recording was taken for 180 min before and after drug injection. After drug injection and EcoG recording, anxiety-depression-like behavior was tested with the open field test for 5 min. RESULTS: The 5 mg/kg DEX significantly reduced the number and duration of SWDs percentage (p < 0.05) between 120 and 180 min, but 25 and 50 mg/kg DEX significantly increased the number and duration of SWDs percentage between 0 and 30 min (p < 0.05), and after 30 min the increase stopped (p > 0.05). And also, the 5 mg/kg DEX decreased the number and duration of SWDs percentage (p < 0.05) for 180 min (p < 0.05), but 25 and 50 mg/kg DEX administration did not alter (p > 0.05). The 5, 25, and 50 mg/kg doses of DEX significantly increased the duration of grooming (p < 0.05) but did not change the number of squares crossed (p > 0.05). CONCLUSION: Low dose DEX reduced absence-like seizures, but care should be taken when using high doses in absence epilepsy. Also, it may be beneficial for painful diseases accompanied by anxiety-depression.

Possible Association of PER2/PER3 Variable Number Tandem Repeat Polymorphism Variants with Susceptibility and Clinical Characteristics in Pancreatic Cancer.

Objective: Pancreatic cancer (PC) is a serious disease with poor outcomes, and its prevalence has been increasing steadily. The circadian rhythm (CR) is involved in multiple physiological events and maintains homeostasis. Alterations in the CR elevate the risk of developing cancer. The present case-control research was carried out to estimate the possible association between PERIOD2/PERIOD3 (PER2/PER3) gene variable number tandem repeat polymorphism (VNTR) variants and PC in the Turkish population. Materials and Methods: A total of 198 subjects (78 patients with PC and 120 healthy controls) were enrolled in this work. Genomic DNA was collected from peripheral blood mononuclear cells, and genotypic analyses was performed using a polymerase chain reaction (PCR) method. Odds ratio (OR) with a 95% confidence interval (95% CI) was calculated using the χ2 test. Results: The frequency of the 4R (4 repeats)/3R (3 repeats), 3R/3R genotypes, and 3R allele of PER2 VNTR in patients with PC was significantly higher than in the control group (p = 0003, p = 0.00004, respectively). PER2 VNTR 4/5 genotype was related to perineural invasion (p = 0.040). The genotype and allele distribution of PER3 VNTR variant did not show any statistical difference between the two groups (p > 0.05). The PER2/PER3 VNTR 4/5-4R/3R combined genotype was increased in the patient group (p = 0.013), while 4/5-4R/4R combined genotype was increased in the control group (p = 0.0001). Conclusions: Our work has indicated that PER2 VNTR 3R allele may play a crucial role in the pathogenesis of PC in Turkish patients, which may become a useful marker for predicting the development of PC. Furthermore, the PER2 VNTR genotype seems to be related to perineural invasion in PC.

On a family of multivariate modified Humbert polynomials.

This paper attempts to present a multivariable extension of generalized Humbert polynomials. The results obtained here include various families of multilinear and multilateral generating functions, miscellaneous properties, and also some special cases for these multivariable polynomials.

Exercise duration rather than peak oxygen uptake better correlates with Fev1 and inspiratory capacity in chronic obstructive pulmonary disease.

BACKGROUND: Exercise duration of constant-load endurance tests has been recently demonstrated to be more sensitive in detecting the changes after bronchodilator administration than either walking distance or peak oxygen uptake in patients with COPD. In the present study, we questioned whether exercise duration of progressive load is better correlated with forced expiratory volume in 1 sec and inspiratory capacity than other indices of submaximal exercise test during stable period in patients with COPD. METHODS: Thirty-three stable COPD patients, and 26 age- and BMI-matched control subjects were recruited. Resting pulmonary function tests and incremental cycle exercise tests were performed. All indices of exercise and pulmonary function tests including exercise duration, peak oxygen uptake (VO(2peak)), and forced expiratory volume in 1 sec (FEV(1)) were recorded. RESULTS: Exercise capacity was lower in COPD than age- and BMI-matched controls as shown by exercise duration and ergometric work (535 +/- 159 vs. 705 +/- 115 sec, p <0.001 and 89.2 +/- 26.6 vs. 117.8 +/- 19.5 W, p <0.001). Statistical analysis revealed that exercise duration slightly better correlates with FEV(1) and inspiration capacity (IC) (R = 0.600, p <0.001; R = 0.615, p <0.001) than peak oxygen uptake (R = 0.284, p >0.05; R = 0.127, p >0.05) in stable period COPD patients. CONCLUSIONS: There is an impairment of aerobic capacity in stable period COPD patients compared to healthy controls. Exercise in COPD patients is ventilation-limited and exercise duration with respect to peak VO(2) is better correlated with FEV(1) and IC in stable COPD patients undergoing progressive-load cycling exercise.