Exploring MicroRNA biogenesis, applications and bioinformatics analysis in livestock: A comprehensive review.

Small non-coding RNAs called microRNAs (miRNAs) control the expression of genes post-transcriptionally. Their correlation with commercial economic traits including milk, meat and egg production, as well as their effective role in animal productivity, fertility, embryo survival and disease resistance, make them significant in livestock research. The miRNAs exhibit distinct spatial and temporal expression patterns, offering insights into their functional roles within cells and tissues. Aberrant miRNA production can disrupt vital cellular processes and genetic networks, contributing to conditions like metabolic disorders and viral diseases. These short RNA molecules are present in extracellular fluids, displaying remarkable stability against RNA degradation enzymes and extreme environmental conditions. miRNAs preservation is facilitated through packaging in lipid vesicles or complex formation with RNA-binding proteins. Numerous studies have illuminated the roles of miRNAs in diverse physiological processes, including embryonic stem cell differentiation, haematopoietic stem cell proliferation and differentiation and the coordinated development of organ systems. The integration of miRNA profiling, next-generation sequencing and bioinformatics analysis paves the way for transformative advancements in livestock research and industry. The present review underscores the applications of miRNAs in livestock, showcasing their potential to improve breeding strategies, diagnose diseases and enhance our understanding of fundamental biological processes.

Cryopreservation alters buffalo sperm kinematics and mitochondrial parameters, acrosome and intra-cellular calcium status.

BACKGROUND: Little is known about the effects of different seasons on the cryopreservation success of buffalo sperm in terms of kinematics and sperm functional parameters. OBJECTIVE: To study the effect of three seasons (winter, comfort and summer) and cryopreservation on sperm kinematics and functional properties in buffalo bulls. MATERIALS AND METHODS: Semen ejaculates (n = 90) collected during three seasons i.e. winter (n = 30), comfort (n = 30), summer (n = 30) were evaluated for sperm kinematics and functional properties. RESULTS: Sperm kinematics with respect to total (TM), progressive (PM) and rapid motility (RM) was higher (P < 0.05) in fresh sperm compared to sperm that had been frozen-thawed. Similarly, all kinematic parameters [viz. average path velocity (VAP), straight linear velocity (VSL), curvilinear velocity (VCL), beats cross frequency (BCF), lateral head displacement (ALH), linearity (LIN) and straightness (STR)] were higher (P < 0.01) at the fresh stage. With respect to season, frozen-thawed semen TM (57.67 ± 115 %), PM (50.2 ± 1.15 %) and RM (51.6 ± 1.19 %) were higher (P < 0.01) when using sperm collected during winter. The stage of cryopreservation (i.e., equilibration and freeze-thawing) also showed significant effects (P < 0.01) on mitochondrial superoxide positive status (MSPS), mitochondrial membrane potential (MMP), acrosome status and intra-cellular calcium status. CONCLUSION: The season of sperm collection and cryopreservation have significant effects on buffalo bull sperm kinematics and functional properties. Doi.org/10.54680/fr24410110612.

Temporal variation and risk factors associated with reproductive disorders in Hardhenu (Bos taurus × Bos indicus) dairy cattle.

This study aimed to investigate the incidence and effect of non-genetic factors on reproductive disorders in the Hardhenu cattle population over a period of 11 years (2010-2021). The study included a total of 1340 cattle for calculating the incidence of reproductive disorders and analysed the occurrence of different reproductive disorders. In the present study, retention of placenta had highest frequency, accounting for approximately 18.36% of the incidence, followed by repeater cows (11.19%), metritis (6.27%), dystocia (0.60%), anestrus (0.45%) and prolapse (0.37%). Chi-square analysis revealed a significant relationship between the year and the incidence of reproductive disorders (p < .05). Logistic regression analysis of temporal variability of reproductive disorders was also analysed, with an increase in the odds from 2014 to 2020, peaking in 2017-2018 and 2018-2019. Logistic regression analysis showed that season and parity did not significantly influence the incidence of reproductive disorders. However, period of calving had a significant impact. Cows calving between 2008 and 2014 had a significantly lower odds ratio (0.13, 95% CI: 0.06-0.30), indicating a decreased risk, while those calving between 2014 and 2017 had a higher odds ratio (0.59, 95% CI: 0.38-0.90), suggesting an increased risk of reproductive disorders. Compared to parity 3, parity 1 (1.344, 95% CI: 0.869-2.08) and parity 2 (1.193, 95% CI: 0.768-1.851) showed highest odds ratio. Similarly, the odds ratio for winter (1.64, 95% CI: 0.93-2.89), summer (1.71, 95% CI: 0.89-3.26) and rainy season (1.64, 95% CI: 0.92-2.91) was higher as compared to autumn. The present results provided valuable insights into the incidence of various reproductive disorders and associated risk factors in Hardhenu cattle. These results can be utilized for targeted interventions to enhance reproductive health and overall productivity in dairy cattle.

Association of CXCR1 gene polymorphism with clinical mastitis, reproductive disorders and performance traits in Hardhenu (Bos taurus × Bos indicus) cattle.

The present study investigated the presence of CXCR1 gene polymorphisms and their association with clinical mastitis, reproductive disorders and performance traits in Hardhenu cattle. Genotyping of the targeted SNP rs211042414 (C>T) at the g.106216468 loci of the CXCR1 gene was performed through PCR amplification and Bsa1 restriction enzyme digestion. The genotypic frequencies revealed three genotypes: CC, CT and TT, with the C allele being the most prevalent. Significant associations were found between the targeted SNP and clinical mastitis occurrence using chi-square and logistic regression analyses. The CC genotype showed higher susceptibility to clinical mastitis with a higher odds ratio of 3.47 compared to TT (1.00) and CT (2.90) genotypes (p < .05). Furthermore, least squares analysis revealed significant associations between genotypes and performance traits such as total milk yield, 305-day milk yield and peak yield (p < .05). The CC genotype exhibited higher milk yields than CT and TT genotypes, indicating a positive association between the C allele and increased milk production. These findings have practical implications for the genetic improvement of Hardhenu cattle. Incorporating the identified CXCR1 gene polymorphisms into existing selection criteria can help enhance disease resistance and milk production traits. However, further validation with a larger sample size is necessary to strengthen the observed associations and ensure their practical applicability.

Genetic analysis for semen quality traits in buffalo bulls.

This study was attempted to estimate the genetic parameters of semen quality traits in buffalo bulls. The study data consisted of 10975 ejaculates from 45 Murrah buffalo bulls (aged 24-72 months) used for breeding program during year 2010 to 2020. Semen quality traits (ejaculate volume, concentration of sperm, mass activity, initial and post-thaw motility, number of sperms per ejaculate, motile sperm number and discard rates) were studied. It was observed that average ejaculate volume was 2.82 ± 1.45 mL with mean concentration of 1040.12 ± 523.26 million/mL. Higher heritability was observed for number of sperms per ejaculate, number of motile sperm and sperm concentration. Significant phenotypic correlation was obtained between volume and number of sperms per ejaculate as well as volume and number of motile sperms. Likewise, significant phenotypic correlation was evident between sperm concentration with sperm number per ejaculate. Highest phenotypic correlation was obtained between sperm count per ejaculate and motile sperm count. Estimated genetic trends showed significant change in volume and motile sperm number. In conclusion, this study ascertains that genetic parameters of semen traits can be considered during the selection of buffalo bulls in breeding program.

Meta-Analysis of Gene Polymorphism of Beta-Lactoglobulin Gene in Indian Dairy Cows.

The aim of the present paper was to summarize the gene polymorphisms of beta-lactoglobulin (BLG) gene and its effects on milk yield in 1840 genotyped Indian dairy cows reported in 17 published studies. The meta-analysis was undertaken using gene frequencies of individual studies under random effects model, whereas for association analysis of genotypes with milk yield, standardized mean differences (SMDs) along with 95% confidence interval (CI) were obtained under four genetic models such as additive (AA vs. BB), dominant (AA+AB vs. BB), completely over dominant (AA+BB vs. AB) and recessive (AA vs. AB+BB). The heterogeneity index (I2) was used to determine heterogeneity between studies. The results of meta-analysis suggested that the pooled allelic frequency of allele A was subsidiary as 0.29 (95% CI 0.24, 0.33, I2 = 88.54%) in targeted population, and also, it was non-significantly (P > 0.05) different between Bos indicus (0.28) and Bos taurus/cross cows (0.30). Egger's test indicated no risk of publication bias (P > 0.05). The results also revealed that BLG gene variants have non-significant (P > 0.05) association with milk yield under all genetic models. Although positive effects of SMDs under some models were observed, however, they failed to meet statistical significance (P > 0.05) due to high heterogeneity between studies which lead to conclusion of only uncertain influences of SNP genotypes with milk yield. It was concluded that BLG markers may not be beneficial for improving milk yield in Indian dairy cows. However, it is suggested that the revalidation of the present results should be done by using more number of studies.

Meta-analysis of Genetic Structure and Association of Prolactin Gene with Performance Traits in Dairy Cattle in India.

The present meta-analysis was carried to provide the more reliable estimates of gene frequency and association of Rsa 1 generated candidate genotype of prolactin gene within exon-3 with performance traits in 1198 Indian dairy cows using data from 15 published studies. Six genetic models viz., codominant (AA vs. AB, AA vs. BB and AB vs. BB), dominant (AA+AB vs. BB), completely over dominant (AA+BB vs. AB) and recessive (AA vs. AB+BB) were used to obtain standardized mean difference (SMD) between genotypes. Meta-analysis showed that the gene frequency of A allele (156 bp) was 0.60 (95% confidence interval (CI) 0.54, 0.65). In association analysis, cows with AB genotype [SMD = 0.65, 95% CI 0.00, 1.30] had significantly (P < 0.05) higher lactation milk yield (LMY) as compared to BB genotype, whereas AA and AB genotypes had similar trend. Likewise, AA + AB also had larger effect [SMD = 2.31, 95% CI 0.21, 4.10] on LMY as compared to BB. Cows with AB genotype had significantly lower age at first calving (AFC) with small effect [SMD (AA vs. AB) = 1.38, 95% CI 0.06, 2.70] and medium effect [SMD (AB vs. BB) = - 3.83, 95% CI - 6.41, - 1.24] as compared to cows with AA and BB genotypes, respectively. This finding was confirmed under dominant and completely over dominant models. In case of fat%, AA genotype showed negative effect (SMD = - 0.51, 95% CI - 0.84, - 0.17) under recessive model. It was concluded that the propagation of allele A is promising to help dairy farmers to improve the genetic quality of their dairy cows.

Recurrent malignant proliferating trichilemmal tumor with lymph node metastasis in a young woman.

Malignant proliferating trichilemmal tumor (MPTT) is a rare cutaneous tumor predominantly affecting the scalp, eyelids, neck and face of elderly women. It is a large, solitary, multilobulated lesion that may arise within a pilar cyst. These tumors are largely benign, often cystic, and are characterized by trichilemmal keratinization. However, at times, the tumor has an aggressive clinical course and a propensity for nodal and distant metastases. Wide local excision with a 1 cm margin of normal tissue is the treatment of choice. Adjuvant chemotherapy and radiotherapy have been occasionally used to prevent recurrence in MPTT. This is a case report of a recurrent malignant trichilemmal tumor over scalp in a young female patient with nodal metastasis.

Meta-analysis of MspI derived variants of growth hormone gene associated with milk yield in dairy cattle.

OBJECTIVE: The present work aimed to obtain common effect sizes for the gene frequency and association of MspI derived variants of growth hormone (GH) gene with milk yield in dairy cows. METHODS: We performed a systematic review and meta-analysis of 35 published studies identified in literature search from 2000 to 2020 (n = 4164). These studies were specific to fragment size (329) for genotypes viz., CC (224, 105 bp), CD (329, 224, 105 bp) and DD (329 bp). Pooled standard mean differences (SMDs) as effect sizes between allele pairs were derived using different genetic models. The heterogeneity between effects sizes across studies was estimated using I2 Index (%). RESULTS: The common effect size for gene frequency of allele C (224, 105 bp) was significantly (P < 0.05) higher in 2881 Bos taurus/cross cows (0.82; 95% CI: 0.74, 0.89; I2 = 97.81%) than 1283 Bos indicus cows (0.15; 95% CI: 0.12, 0.18; I2 = 71.90%), with overall gene frequency was 0.33 (95% CI: 0.21, 0.46; I2 = 99.29%). Additive (CC vs. DD) and dominant (CC + CD vs. DD) did not revealed significant (P > 0.05) association with milk yield. However, completely over dominant (CC + DD vs. CD) and recessive (CC vs. CD + DD) models showed significant (P < 0.05) and positive SMDs with milk yield specially at early lactations. There was no evidence of heterogeneity (I2 = 0.00%) between SMDs across studies. CONCLUSIONS: This meta-analysis suggested potential association of C allele for enhancing milk production of dairy cows.

Clinical Diagnosis and Therapeutic Management of Trypanosoma theileri Infection Associated with Peritonitis in Crossbred Cow: A Rare Case Report.

PURPOSE: The present study reports a very rare case of Trypanosoma theileri like infection in the peritoneal fluid of a 6-year-old female Holstein Friesian (HF) cattle brought to Veterinary Clinical Complex, Lala Lajpat Rai University of Veterinary and Animal Sciences (LUVAS), Hisar. The aim of the clinical study was to report an unusual case of T. theileri-like infection associated with peritonitis and its therapeutic management. METHODS: For confirmatory diagnosis, peritoneal fluid and blood sample was collected from animal for haemato-biochemical examination, buffy coat examination and detection of Trypanosoma antigen by monoclonal antibody-based latex agglutination test. RESULTS: Animal had history of anorexia, high fever, oedematous swelling on the abdominal area and decrease in milk yield since 1 week. Clinical examination revealed high fever, congested conjunctival mucus membrane and oedematous inflammatory swelling on the abdominal region. Haematological examination on Day 1 revealed relative neutrophilia and eosinophilia, whereas other parameters measured were on the lower side of normal range. Thin blood smear examination did not reveal any parasite on first attempt. However, after confirmation of Trypanosoma species in peritoneal fluid collected by FNAC, buffy coat examination of blood sample was also found positive for Trypanosoma species. On Day 2, haematological examination revealed neutrophilic leucocytosis, eosinophilia and anaemia. Blood sample was also found serologically positive for Trypanosoma antigen by monoclonal antibody based latex agglutination test. Biochemical examination revealed increased blood urea nitrogen (BUN), gamma glutamyl transferase (GGT) levels, hyperglycemia, hyperprotienemia and decreased levels of sodium and chloride ions. Animal was primarily treated with isometamidium chloride (Nyzom®) @ 0.5 mg/kg body weight (IM, single dose) along with supportive therapy. CONCLUSION: Animal showed clinical recovery after 10 days of treatment. Post-recovery, blood sample of the animal was re-examined for parasite and other blood parameters and it was found negative for presence of Trypanosoma infection along with restoration of haematological values. Hence, the present study concludes the confirmatory diagnosis and therapeutic use of isometamidium hydrochloride along with anti-inflammatory drugs to Trypanosoma infection.

'Semen dilution effect' on sperm variables and conception rate in buffalo.

The study aim was to determine how to minimize effects of buffalo semen dilution by evaluating the use of egg yolk (EY), low-density lipoprotein (LDL), and OptiXcell (OC) extenders. Ejaculates (n = 18 from six bulls) were divided into three aliquots that were diluted separately with EY, LDL, and OC extenders corresponding to 20 million (M), 12 M, and 2 M sperm/dose, respectively, and cryopreserved. There were a lesser sperm motility, plasma membrane integrity, and percentage un-capacitated sperm with the 2 M sperm/dose, however, the LDL extender was more effective than OC and EY extender for cryopreservation of buffalo sperm. Excess semen dilution resulted in sustained sperm velocities (curvilinear velocity, average path velocity, and straight linear velocity), and these were greater with use of the OC than LDL and EY extenders. There was no change in amplitude of sperm lateral head displacement (ALH) with respect to dilution, but with regard to extender effects, ALH was greater in sperm extended in LDL and OC than EY. Semen dilution to 2 M sperm/dose resulted in a greater mitochondrial superoxide production. Conception rate (CR) was unaffected with 20 and 12, however, with the 2 M sperm/dose dilutions there was a lesser CR. In conclusion, buffalo semen dilution to the extent of 12 M sperm/dose did not affect most of the seminal variables and CR. Using LDL extender at 2 M sperm/dose protected sperm from the 'semen dilution effect' to a greater extent than with use of EY and OC extenders.

Polymorphism of melatonin receptor (MTNR1A) gene and its association with seasonal reproduction in water buffalo (Bubalus bubalis).

The water buffalo have a seasonal pattern of reproduction with decreased sexual activity during the longer photoperiod. The present study was designed to identify a single nucleotide polymorphism (SNP) in the MTNR1 A gene and its association with seasonal reproduction and reproductive characteristics in Murrah buffalo cows. The 812 bp fragment encompassing exon II of the MTNR1 A gene was amplified from genomic DNA of 190 pluriparous Murrah buffalo cows. Amplified PCR products from 12 samples were subjected to custom sequencing of both ends (5' and 3' ends). A synonymous mutation was identified at position 72 in exon II of MTNR1 A gene. Digestion of PCR products with HpaI enzyme indicated there was one polymorphic site caused by the presence of nucleotide C at position 72 in place of T that resulted in three genotypes: T/T (812bp), C/T (812, 743 and 69 bp) and C/C (743 and 69 bp). There was an association (P < 0.05) between the MTNR1 A genotype and reproductive activity in Murrah buffalo cows such that buffalo cows with T/T genotype had less seasonal reproductive activity as compared with those with the C/C genotype. The period of greatest mating activity of buffalo cows with the C/C genotype was from November to December whereas buffalo cows with the T/T genotype mated mainly between May and July. Thus, the polymorphism of the MTNR1 A gene might be considered as a genetic marker to identify Murrah buffalo, which are able to reproduce during periods that are not a part of the typical breeding season for these buffalo.

p38 MAPK signaling in oral-related diseases.

Multiple dental diseases are characterized by chronic inflammation, due to the production of cytokines, chemokines, and prostanoids by immune and non-immune cells. Membrane-bound receptors provide a link between the extracellular environment and the initiation of intracellular signaling events that activate common signaling components, including p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor (NF)-kappaB. Although ERK pathways regulate cell survival and are responsive to extracellular mitogens, p38 MAPK, JNK, and NF-kappaB are involved in environmental stress responses, including inflammatory stimuli. Over the past decade, significant advances have been made relative to our understanding of the fundamental intracellular signaling mechanisms that govern inflammatory cytokine expression. The p38 MAPK pathway has been shown to play a pivotal role in inflammatory cytokine and chemokine gene regulation at both the transcriptional and the post-transcriptional levels. In this review, we present evidence for the significance of p38 MAPK signaling in diverse dental diseases, including chronic pain, desquamative disorders, and periodontal diseases. Additional information is presented on the molecular mechanisms whereby p38 signaling controls post-transcriptional gene expression in inflammatory states.

Study of the dairy characters of lactating Murrah buffaloes on the basis of body parts measurements.

AIM: The aim of the study was to correlate the milk yield of Murrah buffaloes with certain body parts measurements. MATERIALS AND METHODS: A total of 70 lactating Murrah buffaloes were selected from Buffalo Farm, Lala Lajpat Rai University of Veterinary and Animal Science, Hisar and were randomly selected in a range from first to fifth parity. Traits studied were 305 days milk yield (MY), body weight (BW), body length (BL), muzzle width (MW), height at wither (HW), abdominal girth (AG), chest girth (CG), body depth fore, body depth rear, hip bone distance (HBD), pin bone distance (PBD), skin thickness (STK), and tail length (TL). Data were collected and statically analyzed by Pearson's correlation method. RESULT: The result of this study showed that Murrah buffaloes had the average 2604.8±39.5 kg for MY, 556.1±4.9 kg for BW, and 152.2±0.8 cm for BL. This study showed that buffaloes had positive significant (p<0.05) correlation between MY and BW (0.26). Highly significant (p<0.01) correlation was observed between MY and AG (0.64), MW (0.42). Significant (p<0.01) negative correlation was observed between MY and STK (-0.79). Different body part measurements (BW, BL, HW, AG, CG, MW, TL, BD, PBD, HBD, STK) were significantly correlated with each other. CONCLUSION: This study can be helpful as a selection tool to enhance and evaluate the production potential by setting standards of Murrah buffalo breed. BW, abdominal growth, muzzle thickness, and STK were found key factors while selecting a dairy Murrah buffalo.

Estimates of genetic parameters for fat yield in Murrah buffaloes.

AIM: The present study was performed to investigate the effect of genetic and non-genetic factors affecting milk fat yield and to estimate genetic parameters of monthly test day fat yields (MTDFY) and lactation 305-day fat yield (L305FY) in Murrah buffaloes. MATERIALS AND METHODS: The data on total of 10381 MTDFY records comprising the first four lactations of 470 Murrah buffaloes calved from 1993 to 2014 were assessed. These buffaloes were sired by 75 bulls maintained in an organized farm at ICAR-National Dairy Research Institute, Karnal. Least squares maximum likelihood program was used to estimate genetic and non-genetic parameters. Heritability estimates were obtained using paternal half-sib correlation method. Genetic and phenotypic correlations among MTDFY, and 305-day fat yield were calculated from the analysis of variance and covariance matrix among sire groups. RESULTS: The overall least squares mean of L305FY was found to be 175.74±4.12 kg. The least squares mean of overall MTDFY ranged from 3.33±0.14 kg (TD-11) to 7.06±0.17 kg (TD-3). The h(2) estimate of L305FY was found to be 0.33±0.16 in this study. The estimates of phenotypic and genetic correlations between 305-day fat yield and different MTDFY ranged from 0.32 to 0.48 and 0.51 to 0.99, respectively. CONCLUSIONS: In this study, all the genetic and non-genetic factors except age at the first calving group, significantly affected the traits under study. The estimates of phenotypic and genetic correlations of MTDFY with 305-day fat yield was generally higher in the MTDFY-5 of lactation suggesting that this TD yields could be used as the selection criteria for early evaluation and selection of Murrah buffaloes.

Genetic analysis of growth traits in Harnali sheep.

AIM: The present investigation was to study genetic characteristics of Harnali sheep with respect to growth performance and to estimate genetic parameters. MATERIALS AND METHODS: The 22 years (1992-2013) data of growth traits of a 1603 synthetic population of Harnali sheep maintained at Lala Lajpat Rai University of Veterinary and Animal Sciences, Hisar, was utilized for this study. A mixed methodology with regression on their dam's weight was used to study the effect of non-genetic factors on growth traits. Heritability, genetic and phenotypic correlations were estimated using paternal half-sib analysis for body weight at various ages and average daily gain (ADG) for different growth periods. RESULT: The overall least squares mean of body weights recorded for birth weight (BW), weaning weight (WW), six months body weight (SMW), one yearling body weight (YBW), average daily gain from birth to 3 months (ADG1) and average daily gain from 3 to 12 months (ADG2) were 3.35±0.05 kg, 12.41±0.08 kg, 16.30±0.12 kg, 21.88±0.08 kg, 100.66±0.86 g/day and 35.07±0.39 g/day, respectively. The effects of year of birth significantly (p<0.01) influenced the BW, WW, SMW, YWB, ADG1 and ADG2. The effects of sex of lamb significantly (p<0.01) influenced the BW, WW SMW, YWB, ADG1 and ADG2. The effects of dam's weight at lambing significantly (p<0.01) influenced BW, WW, SMW, YWB, ADG1 and ADG2. No definite trend was observed over the years for the averages of body weight and gain. The heritability estimates of BW, WW, SMW, YBW, ADG1 and ADG2 were 0.40±0.05, 0.38±0.05, 0.45±0.06, 0.29±0.05, 0.40±0.06 and 0.33±0.02, respectively. The male lambs were significantly heavier than females at all stages of growth. The heritability estimates were moderate for all the growth traits and high genetic correlations of BW and WW with SMW were found. CONCLUSION: Due to high heritability and positive correlations of SMW with other body weights and daily gain, it was concluded that selection on the basis of SMW would be the best approach to improve growth performance in Harnali sheep.

Protective effects of nimesulide (COX Inhibitor), AKBA (5-LOX Inhibitor), and their combination in aging-associated abnormalities in mice.

Several inflammatory processes play a critical role in brain aging and are associated with increased vulnerability to neurodegeneration. Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX), two enzymes involved in the oxygenation of the arachidonic acid, are upregulated in the central nervous system during aging and are associated with different aging-related brain pathologies. The present experiment was performed to study the effects of 5-LOX inhibitor, acetyl-11-keto-beta-boswellic acid (AKBA), nimesulide (preferential COX-2 inhibitor), and their combination on cognitive performance of young and aged mice, using elevated plus maze test. Chronic administration of AKBA (100 mg/kg, p.o.) and nimesulide (2.42 mg/kg, p.o.) for 15 days significantly reversed the aging-induced retention deficit in mice. Coadministration of AKBA and nimesulide enhanced the cognitive performance in aged mice when compared with that in per se treatment. The aging-related increase in oxidative damage (increased LPO and decreased GSH) was reversed by AKBA, nimesulide, and their combination. Further, per se COX and LOX inhibitors and their combination did not produce any alteration in gastrointestinal parameters; they also reversed the aging-induced motor dysfunction in the aged animals. On the basis of these observations, present findings indicated that the combination of COX and LOX inhibitors (dual inhibitors) may provide a new therapeutic innovation for the treatment of aging-related brain disorders such as Alzheimer's disease and different motor dysfunctions with adequate gastrointestinal tolerability.

Optimizing age of bull at first use in relation to fertility of Murrah breeding bulls.

AIM: The aim of the present investigation was to optimize the age at first use (AAFU) of semen of Murrah breeding bulls, which will help in early selection of bulls under progeny testing program for improving the reproductive performance in the herd. MATERIALS AND METHODS: The data on AAFU, conception rate based on first A.I. (CRFAI), overall conception rate (OCR), and birth weight (B.WT) of 57 Murrah bulls during 1993-2014 at NDRI center pertaining to 14 sets of Network Project on Buffalo Improvement at ICAR-National Dairy Research Institute, Karnal, Haryana, India were adjusted for significant environmental influences and subsequently analyzed. Simple and multiple regression models were used for prediction of CRFAI and OCR of Murrah breeding bulls. Comparative evaluation of three developed models (I-III) showed that Model III, having AAFU and B.WT, fulfill the accuracy of model as revealed by high coefficient of determination, low mean sum of squares due to error, low conceptual predictive value, and low Bayesian information criterion. RESULTS: The results revealed that the average predicted CRFAI was highest (39.95%) at <3.5 years and lowest (34.87%) at >4.5 years of age at first A.I/use. Similarly, average predicted OCR was highest (41.05%) at <3.5 years and lowest (39.42%) at >4.5 years of age at first A.I/use of Murrah bulls. CONCLUSION: In organized herd under progeny testing program, Murrah bulls should be used at young age, i.e. prior to 3.5 years, which is expected to result in 5.08% better CRFAI and 1.63% better OCR in comparison to Murrah bulls used after 4.5 years of age.

Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice.

Inflammation processes may play a critical role in the pathogenesis of the degenerative changes and cognitive impairments associated with Alzheimer's disease (AD). Non-steroidal anti-inflammatory drugs are reported to be effective in reducing the risk of developing AD or cognitive impairments. Present experiments were performed to study the possible effect of various NSAIDs on cognitive performance of young, aged and scopolamine or lipopolysaccharide (LPS) treated mice (an animal model of AD) using one trial step through type of passive avoidance and in elevated plus maze task. Chronic administration of NSAIDs at the ED(50) doses (nimesulide, rofecoxib and naproxen for 15 days) significantly reversed the age or scopolamine-induced retention deficits in both test paradigms. However, in both the memory paradigms chronic administration of NSAIDs failed to modulate the retention performance of young mice. Acute administration of LPS (50 mcg/mouse, i.p.) significantly exhibited retention deficits after 24 h and seventh day of its administration in both test paradigms. Chronic administration (7 days) of rofecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor (1.92 mg/kg, p.o.) significantly reversed the LPS-induced retention deficits in both tests. The results of this study showed chronic treatment of NSAIDs reverses the cognitive deficits in age and scopolamine or LPS treated mice. These findings establish a link between the central nervous system expression of various pro-inflammatory cytokines and learning impairment in mice.

Sildenafil-induced peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway.

Although several lines of evidence have shown a role of the nitric oxide/cyclic guanosine monophosphate signaling pathway in the nociceptive mechanism, the exact role of the phosphodiesterase (PDE) 5 enzyme via the NO-cGMP pathway is not fully understood in pain response. The present study was aimed at exploring the role of the NO-cGMP pathway in nociceptive conditions in experimental animals. Peripheral nociception was assessed by acetic acid-induced chemonociception or carrageenan-induced hyperalgesia and central nociception was assessed by tail-flick and hot-plate methods. Sildenafil exhibited dose-dependent (1, 2, 5 and 10 mg/kg, i.p.) antinociception in both male and female mice against acetic acid-induced writhing. However, it did not alter the pain threshold in central nociception (5 and 10 mg/kg, i.p.). Local administration of sildenafil (50-200 microg/paw, i.pl) also attenuated carrageenan-induced hyperalgesia. In the peripheral nociceptive reaction (acetic acid-induced chemonociception), the antinociceptive effect of sildenafil (2 mg/kg, i.p.) was enhanced by co-administration of sodium nitroprusside (0.25 mg/kg), and L-arginine (50 mg/kg). Sildenafil-induced analgesia was significantly blocked by methylene blue (1 mg/kg), a guanylate cyclase inhibitor, but was not reversed by L-NAME (10 mg/kg), a nitric oxide synthase inhibitor. But a higher dose of L-NAME (20 mg/kg) significantly reversed sildenafil analgesia. Both of these agents also reversed the facilitatory effect of L-arginine (50 mg/kg) and sodium nitroprusside (0.25 mg/kg) on sildenafil analgesia. These results suggest that sildenafil-induced analgesia is mediated via the inhibition of PDE5. The results also indicate that the guanylate cyclase system is stimulated in the peripheral nociceptive reaction. In conclusion, sildenafil produces antinociception and its effect can be potentiated by sodium nitroprusside and L-arginine, probably through the activation of the NO-cyclic GMP pathway.