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ε-Poly-L-lysine (ε-PL) is a homopolymer linked by the peptide bond between the carboxylic and the epsilon amino group of adjacent lysine molecules. It is naturally occurring, water soluble, biodegradable, edible and nontoxic towards humans and environment. ε-PL shows a wide range of antimicrobial activity and is stable at high temperatures. This review focuses on various ε-PL producing strains, screening procedure, production, synthesis, antimicrobial activity, and its various applications in food industry. [ABSTRACT FROM AUTHOR]

Laccases (benzenediol:oxygen oxidoreductase, EC 1.10.3.2) are multi-copper oxidases that are widely distributed among plants, insects, and fungi. They have been described in different genera of ascomycetes, some deuteromycetes, and mainly in basidiomycetes. These enzymes catalyze the one-electron oxidation of a wide variety of organic and inorganic substrates, including mono-, di-, and polyphenols, amino-phenols, methoxyphenols, aromatic amines, and ascorbate, with the concomitant four electron reduction of oxygen to water. Laccase is currently the focus of much attention because of its diverse applications, such as delignification of lignocellulosics, crosslinking of polysaccha-rides, bioremediation applications, such as waste detoxification, and textile dye transformation, food technologic uses, personal and medical care applications, and biosensor and analytical applications. This review helps to understand the properties of this important enzyme for efficient utilization for its biotechnological and environmental applications.

Background: Polygenic risk scores (PRS) derived from European individuals have reduced portability across global populations, limiting their clinical implementation at worldwide scale. Here, we investigate the performance of a wide range of PRS models across four ancestry groups (Africans, Europeans, East Asians, and South Asians) for 14 conditions of high-medical interest., Methods: To select the best-performing model per trait, we first compared PRS performances for publicly available scores, and constructed new models using different methods (LDpred2, PRS-CSx and SNPnet). We used 285 K European individuals from the UK Biobank (UKBB) for training and 18 K, including diverse ancestries, for testing. We then evaluated PRS portability for the best models in Europeans and compared their accuracies with respect to the best PRS per ancestry. Finally, we validated the selected PRS models using an independent set of 8,417 individuals from Biobank of the Americas-Genomelink (BbofA-GL); and performed a PRS-Phewas., Results: We confirmed a decay in PRS performances relative to Europeans when the evaluation was conducted using the best-PRS model for Europeans (51.3% for South Asians, 46.6% for East Asians and 39.4% for Africans). We observed an improvement in the PRS performances when specifically selecting ancestry specific PRS models (phenotype variance increase: 1.62 for Africans, 1.40 for South Asians and 0.96 for East Asians). Additionally, when we selected the optimal model conditional on ancestry for CAD, HDL-C and LDL-C, hypertension, hypothyroidism and T2D, PRS performance for studied populations was more comparable to what was observed in Europeans. Finally, we were able to independently validate tested models for Europeans, and conducted a PRS-Phewas, identifying cross-trait interplay between cardiometabolic conditions, and between immune-mediated components., Conclusion: Our work comprehensively evaluated PRS accuracy across a wide range of phenotypes, reducing the uncertainty with respect to which PRS model to choose and in which ancestry group. This evaluation has let us identify specific conditions where implementing risk-prioritization strategies could have practical utility across diverse ancestral groups, contributing to democratizing the implementation of PRS., (© 2024. The Author(s).)

Cancer patients suffer from complicated chemotoxicity. Pharmacogenomics can help stratify patients by predicting their response to treatment and susceptibility toward severe side effects. The spindle-assembly checkpoint (SAC) is an important pathway that is activated by platinum and taxane compounds and plays a crucial role in their cytotoxic activity. This study investigated a SAC component, Budding Uninhibited by Benzimidazoles 3 (BUB3), its expression, and genetic variants in advanced ovarian cancer patients treated with paclitaxel-carboplatin chemotherapy. Among 80 patients, BUB3 expression correlated with chemosensitivity, suggesting its potential as a predictive marker for chemotherapy response. However, high BUB3 expression was associated with a higher risk of poor survival. In addition, genetic polymorphisms in BUB3 (rs11248416 and rs11248419) were significantly linked to chemotherapy-related toxicities, with rs11248416 showing a negative impact on the patient's physical quality of life., (Copyright © 2024 Copyright: © 2024 Indian Journal of Public Health.)

Aim: To evaluate the feasibility and efficacy of switching to a self-sampling based screening as compared to ongoing provider-collection based screening using HPV DNA test and assess the compliance of HPV positive women for further treatment during the COVID 19 pandemic., Method: The study participants were women aged 30-60 years from rural and semi-urban communities around Kolkata, who underwent screening followed by HPV testing by Hybrid Capture II test. In the pre pandemic era, the women who attended the health centres where trained health workers that collected cervical samples. Following lockdown, the health workers distributed the self-sampling device to the women during home visits and counselled them to collect their samples by themselves. Thereafter the self collected screened positive women were brought to the hospital for further treatment instead of community clinics., Results: From April 2018 to March 2020, 12,718 women underwent screening using either HPV DNA test or visual inspection with acetic acid. HPV samples were either provider collected (62.7%) or self-collected (37.2%). The HPV positivity and CIN2+ detection rate were 5.4% and 2%. From April 2020 to February 2022, 10,792 women underwent screening using self-sampling only. The HPV positivity rate and CIN2+ detection rate were found to be 5.1% and 1.9 % ., Conclusion: Cervical cancer screening by HPV self-sampling advocates participation of more women especially in rural areas, while accelerating progress towards elimination of cervical cancer.

Significance: Cross-talk with TTEX CD8+ T cells mediated by the VEGFR2 axis induces aggressive properties in cancer stem cells to promote tumor progression., (©2023 American Association for Cancer Research.)

Among the different anthropogenic stimuli humans are exposed to, the psychological and cardiovascular effects of auditory stimuli are less understood. This study aims to explore the possible range of change after a single session of auditory stimulation with three different ‘Modes’ of musical stimuli (MS) on anxiety, biomarkers of stress, and cardiovascular parameters among healthy young individuals. In this randomized control trial, 140 healthy young adults, aged 18−30 years, were randomly assigned to three MS groups (Mode/Raga Miyan ki Todi, Malkauns, and Puriya) and one control group (natural sounds). The outcome measurements of the State-Trait Anxiety Inventory, salivary alpha-amylase (sAA), salivary cortisol (sCort), blood pressure, and heart rate variability (HRV) were collected at three time points: before (M1), during (M2), and after the intervention (M3). State anxiety was reduced significantly with raga Puriya (p = 0.018), followed by raga Malkauns and raga Miyan Ki Todi. All the groups showed a significant reduction in sAA. Raga Miyan ki Todi and Puriya caused an arousal effect (as evidenced by HRV) during the intervention and significant relaxation after the intervention (both p < 0.005). Raga Malkauns and the control group had a sustained rise in parasympathetic activity over 30 min. Future studies should try to use other modes and features to develop a better scientific foundation for the use of Indian music in medicine.

Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits., Competing Interests: M.J.D. is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and a consultant for Camp4 Therapeutics, Takeda Pharmaceutical, and Biogen. The spouse of C.J.W. works at Regeneron Pharmaceuticals. C.-Y.C. is employed by Biogen. C.R.G. owns stock in 23andMe, Inc. T.R.G. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. E.E.K. has received speaker fees from Regeneron, Illumina, and 23andMe and is a member of the advisory board for Galateo Bio. R.E.M. has received speaker fees from Illumina and is a scientific advisor to the Epigenetic Clock Development Foundation. G.D.S. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. K.S. and U.T. are employed by deCODE Genetics/Amgen, Inc. J.Z. has received research funding from various pharmaceutical companies to support the application of Mendelian randomization to drug target prioritization. S.M. is a co-founder of and holds stock in Seonix Bio., (© 2022.)

Introduction: A major challenge to enabling precision health at a global scale is the bias between those who enroll in state sponsored genomic research and those suffering from chronic disease. More than 30 million people have been genotyped by direct-to-consumer (DTC) companies such as 23andMe, Ancestry DNA, and MyHeritage, providing a potential mechanism for democratizing access to medical interventions and thus catalyzing improvements in patient outcomes as the cost of data acquisition drops. However, much of these data are sequestered in the initial provider network, without the ability for the scientific community to either access or validate. Here, we present a novel geno-pheno platform that integrates heterogeneous data sources and applies learnings to common chronic disease conditions including Type 2 diabetes (T2D) and hypertension., Methods: We collected genotyped data from a novel DTC platform where participants upload their genotype data files and were invited to answer general health questionnaires regarding cardiometabolic traits over a period of 6 months. Quality control, imputation, and genome-wide association studies were performed on this dataset, and polygenic risk scores were built in a case-control setting using the BASIL algorithm., Results: We collected data on N = 4,550 (389 cases / 4,161 controls) who reported being affected or previously affected for T2D and N = 4,528 (1,027 cases / 3,501 controls) for hypertension. We identified 164 out of 272 variants showing identical effect direction to previously reported genome-significant findings in Europeans. Performance metric of the PRS models was AUC = 0.68, which is comparable to previously published PRS models obtained with larger datasets including clinical biomarkers., Discussion: DTC platforms have the potential of inverting research models of genome sequencing and phenotypic data acquisition. Quality control (QC) mechanisms proved to successfully enable traditional GWAS and PRS analyses. The direct participation of individuals has shown the potential to generate rich datasets enabling the creation of PRS cardiometabolic models. More importantly, federated learning of PRS from reuse of DTC data provides a mechanism for scaling precision health care delivery beyond the small number of countries who can afford to finance these efforts directly., Conclusions: The genetics of T2D and hypertension have been studied extensively in controlled datasets, and various polygenic risk scores (PRS) have been developed. We developed predictive tools for both phenotypes trained with heterogeneous genotypic and phenotypic data generated outside of the clinical environment and show that our methods can recapitulate prior findings with fidelity. From these observations, we conclude that it is possible to leverage DTC genetic repositories to identify individuals at risk of debilitating diseases based on their unique genetic landscape so that informed, timely clinical interventions can be incorporated., (© 2022. The Author(s).)

Background: Ovarian cancer (OvCa), the deadliest gynaecological malignancy, is associated with poor prognosis and high mortality rate. Ovarian cancer has been related with CA-125 and metabolic reprogramming by SIRT1 leading to metastasis with the involvement of exosomes., Methods: Clinicopathological data of OvCa patients were collected to perform the analysis. Patients' samples were collected during surgery for immunohistochemistry and flow cytometric analysis of SIRT1, HIF-1 α , exosomal markers (CD81 and CD63), ki-67, and PAS staining for glycogen deposition. Adjacent normal and tumor tissues were collected as per the CA-125 levels., Results: CA-125, a vital diagnostic marker, has shown significant correlation with body mass index (BMI) ( P = 0.0153), tumor type ( P = 0.0029), ascites level, ascites malignancy, degree of dissemination, tumor differentiation, FIGO stage, TNM stage, laterality, and tumor size at P < 0.0001. Since significant correlation was associated with BMI and degree of dissemination, as disclosed by IHC analysis, metabolic marker SIRT1 ( P = 0.0003), HIF-1 α ( P < 0.0001), exosomal marker CD81 ( P < 0.0001), ki-67 status ( P = 0.0034), and glycogen deposition ( P  <0.0001) were expressed more in tumor tissues as compared to the normal ones. ROC analysis of CA-125 had shown 327.7 U/ml has the best cutoff point with 82.4% sensitivity and specificity of 52.3%. In addition, Kaplan-Meier plots of CA-125 ( P < 0.0001), BMI ( P = 0.001), degree of dissemination ( P < 0.0001), and ascites level ( P  <0.0001) reflected significant correlation with overall survival (OS). Upon multivariate Cox-regression analysis for overall survival (OS), BMI ( P = 0.008, HR 1.759, 95% CI 1.156-2.677), ascites malignancy ( P = 0.032, HR 0.336, 95% CI 0.124-0.911), and degree of dissemination ( P = 0.004, HR 1.994, 95% CI 1.251-3.178) were significant proving to be independent indicators of the disease., Conclusion: Clinicopathological parameters like BMI, degree of dissemination, and ascites level along with CA-125 can be prognostic factors for the disease. Levels of CA-125 can depict the metabolic and metastatic factors. Thus, by targeting SIRT1 and assessing exosomal concentrations to overcome metastasis and glycogen deposition, individualized treatment strategy could be designed. In-depth studies are still required., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Sraddhya Roy et al.)

Purpose: The study aims to record the quality of life (Qol) and its changes while ovarian cancer (OC) patients undergo debulking surgeries and chemotherapy in a tertiary care hospital of Eastern India., Methods: Patients with advanced epithelial OC (FIGO stages III-IV) were recruited. They underwent primary/interval debulking surgeries with classical chemotherapy (adjuvant/neoadjuvant) of intravenous tri-weekly doses of paclitaxel + carboplatin. QoL was assessed using Fact- O + FACIT-Sp-12 questionnaire with a set of 51 questions in different domains (spiritual, physical, social, emotional, and functional factors) and a special set for OC patients under the heading "Additional concerns." The responses from patients were recorded at baseline (diagnosis/study entry), 2, 4, and 6 months during the treatment visits. Overall survival (OS) was assessed using Kaplan Meier curve., Results: A majority of patients were 49.15±10.8 years of age, school-educated (54%), unemployed/homemakers (73.5%), belonging from rural setup (64.6%) with a monthly income of Rs. 2000/- to Rs. 5000/-. There was no statistically significant (p>0.05) improvement found in Qol from the baseline till the end of the study, neither overall nor in subsets (responders (Rs)/partial responders (PRs)/non-responder (NRs) groups or the adjuvant and neoadjuvant chemotherapy groups). The common toxicities like anemia, constipation, and weight loss were significantly (p<0.05) correlated with the patients' physical, functional, emotional, and social well-being., Conclusion: Ovarian cancer patients represent a poor functional, social, and disease-specific quality of life that needs to be addressed, identified, and improved by the growing nexus of healthcare providers and researchers., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aim: Advanced epithelial ovarian cancer (OC) has a high disease manifestation with difficult-to-manage symptoms that limit the patients' functionality. Abdominal pain, persistent back pain, and neuropathic pain are among the common discomforts associated with OC and its treatment. Our study aims to determine pain scores in advanced OC patients undergoing surgery and chemotherapeutic treatment with carboplatin and paclitaxel., Methods: One hundred and ten patients with advanced epithelial OC were enrolled and treated with surgery and an adjuvant/neoadjuvant chemotherapy regimen of carboplatin-paclitaxel for six cycles (triweekly). Pain intensity was analyzed using the validated numerical rating scale for resting, movement, sleep interference-associated pain, and neuropathic pain scores were evaluated using the neuropathic pain symptom inventory scale. Pain was correlated with Qol according to Fact-O questionnaires. Chemo-response was evaluated using the CA125 blood biomarker and CT scan of the abdomen and thorax. Data were recorded at baseline, 2, 4, and 6 months of the six chemotherapy cycles., Results: Of the 110 patients, no statistically significant differences were found in pain at baseline and after treatment ( P > 0.05) and between the responder and non-responder categories ( P > 0.05). However, movement-associated pain had a significant correlation with chemo-response and a strong positive correlation with the patients' physical and functional wellbeing. There were more chemo-induced neuropathy occurrences ( P = 0.001) in the neoadjuvant chemotherapy group., Conclusion: Patients in the neoadjuvant chemotherapy arm experienced more chemo-induced neuropathy that was persistent and did not improve with the treatment., Relevance for Patients: Peripheral neuropathy is a common adverse effect of platinum and taxane chemotherapeutic drugs that persists throughout cancer treatment and in survivorship. This research provides evidence that chemotherapy-associated neuropathy affects Qol of patients and it will be helpful to improve pain and palliative care management policies., Competing Interests: The authors declare no conflict of interest., (Copyright: © Whioce Publishing Pte. Ltd.)

Background: Initial introduction of HPV vaccination from 2006 to 2008 was largely confined to high-income countries (HIC), such as Australia, the United States, and Europe, where cervical cancer incidence is lowest. Much of the post-introduction literature has come from HICs, with a focus on coverage levels achieved, provider acceptability and early impact of vaccination on disease endpoints. However, there are a few literature evaluating the mechanics of delivery, feasibility of the health system and acceptability from low and middle income countries (LMICs). The primary objective was to evaluate the feasibility, acceptability and safety of two dose HPV vaccination in adolescent girls between 9-14 years., Methods: After an orientation camp followed by filling up of prevaccine questionnaires by parents on HPV related diseases and its vaccines and informed consent, girls between9-14years were vaccinated. They were asked to report any side effects in the next 24 hours after each dose. Parents were contacted on Day 7 and Day 30 to enquire about any side effects . Total 3 visits were required i.e two for the vaccination and one visit at 7th month post completion of second dose. To estimate the acceptability, successful completion of two doses by at least 80% of the girls were measured. For measurement of acceptability, either of the parents were recalled along with their daughter at 7th month and were asked to fill up a pre-set questionnaire., Results: After institutional ethical clearance, 555 girls were recruited in the study from rural parts of West Bengal, India between July, 2017 to November, 2017. Out of which, 544 girls (98%) received their 2nd dose between January, 2018 and May, 2018 without any serious adverse effects. No serious adverse effect was reported on follow up till December, 2019., Conclusion: The introduction of HPV vaccination is feasible in large scale and the vaccine is well accepted and safe., .

Interpretation of histopathology of cervical premalignant lesions suffers from marked interobserver variability due to its subjective nature. We aimed to evaluate the usefulness of the biomarkers p16 and Ki-67 in improving the diagnostic accuracy of cervical histopathology and assess the correlation between p16 expression and human papillomavirus test in different grades of cervical intraepithelial neoplasia (CIN). Cervical tissue specimens with a diagnosis of CIN 1 or worse (CIN 1+) on hematoxylin and eosin staining were selected for immunohistochemistry (IHC) staining for p16 and Ki-67. The IHC slides were examined by a gynecologic pathologist along with a review of hematoxylin and eosin slides. The review histopathology diagnosis was used to correlate with the IHC results. We observed that the proportion of women with overexpression of p16 increased with increasing histologic severity: 0% in women with normal histology; 33.3% in women with CIN 1; 58.1% in women with CIN 2; and 73.8% in women with CIN 3. Among the human papillomavirus-positive women, 76.3% (58/76) women with CIN 2/CIN 3 expressed p16, and only 8.9% (4/45) women with normal histopathology or CIN 1 expressed the same. A combination of p16 positivity and abnormal expression of Ki-67 beyond the lower third of the epithelium was observed in 0% of normal/CIN 1 and 60.5% (40/66) of CIN 3 detected on routine histopathology. We concluded that dual staining could be used as an adjunctive test to improve the diagnostic accuracy of histopathology. In addition, p16/Ki-67 IHC has a role in guiding management decisions in cases with discordant colposcopy and histopathology diagnoses.

Background: Breast cancer is the most common cancer in Indian women., Aim: The aim of the study was to report the sociodemographic factors, habits, personal history, gynecological and obstetric history, the clinical presentation of Indian women, and analyze those factors with the diagnosis of breast cancer., Methods: This study is based on retrospective data collection from case files of women who attended the Cancer Detection Centre during January1995-September 2016., Results: Data analysis for 1196 women showed 31.5% aged between 26 and 35 years; 90.7% were Hindus; 61.3% school-educated; 77.0% housewives/unemployed; 80.6% married and 98.2% were non-vegetarian. Physical activity, medical history and gynecologic history of menarche, menstrual type, menopause, marital age, and breast feeding history had a strong correlation with clinical diagnosis (p<0.05). About 8.4% of the total population was diagnosed with breast cancer using smear cytology, FNAC, mammography, and USG., Conclusions: Age, lack of proper education, marital status, food habit, physical activity, age of menarche, menstrual type, menopause, marital age, and breastfeeding history were highlighted as significant risk factors of breast cancer in Indian women. Smears from nipple discharges, FNAC, mammography, and USG are effective methods for breast cancer detection in low-cost setting where routine organized screening programs are not available., Relevance for Patients: The study will identify important risk factors among women in the Eastern region of India. Thus, background information of patients can be used to emphasize the importance of organizing breast cancer screening while making public health policies and implementing breast cancer control programs., Competing Interests: There are no conflicts of interest among the authors., (Copyright © 2020, Whioce Publishing Pte. Ltd.)

Background: Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are becoming a major cause of chronic liver diseases globally. Polyunsaturated fatty acids (PUFA) have been postulated as a potential treatment for NAFLD. They can be obtained from diet and are also endogenously synthesized by enzymes delta-6-desaturase (D6D), delta-5-desaturase, and elongases. The current study is aimed at investigating the differences in the intake and levels of plasma PUFA between NAFLD patients and controls in Asian Indians. This correlation further propelled a pilot study to check for the differences in the gut microbiome of NASH subjects versus controls., Methods: One hundred forty-seven subjects were recruited and were grouped into healthy controls and cases. Subjects filled a food frequency questionnaire to assess PUFA intake. Plasma samples were subjected to gas chromatography analysis. For characterizing the gut microbiome, fecal samples of 20 NASH and healthy controls were analyzed by 16s rRNA gene sequencing. Alpha and beta diversity metrics and taxonomic analysis were carried out., Results: Plasma levels of eicosapentaenoic acid, γ-linoleic acid and D6D enzyme activity were significantly lower in cases. Dietary intake of total n-6 and n-3 PUFA did not differ between the two groups. Relative abundance of Streptococcus and Clostridium ramosum was significantly higher in NASH patients compared with healthy controls., Conclusion: This study demonstrates, for the first time, decreased D6D enzyme activity and plasma PUFA levels in NAFLD patients. Furthermore, it demonstrates gut dysbiosis in histologically proven NASH patients vis-à-vis healthy controls.

Introduction: Uterine rupture is a catastrophic obstetrical emergency associated with a significant feto-maternal morbidity and mortality. Many risk factors for uterine rupture, as well as a wide range of clinical presentations, have been identified., Objectives: To analyze the frequency, predisposing factors, and maternal and fetal outcomes of uterine rupture., Methods: A retrospective analysis of cases of unscarred uterine rupture was conducted at the Department of Obstetrics and Gynecology, RIMS, Imphal from June 1, 2010 to June 30, 2012., Results: Our analysis comprised 13 cases. Of these, 30.8 % were booked cases. Most of the cases (46.2 %) were Para 2. Uterine rupture occurred at term in 10 cases. The rupture occurred due to mismanaged labor (30.8 %), the use of oxytocin (23 %), instrumental delivery (15.4 %), obstructed labor (15.4 %), induction by prostaglandin gel (7.7 %), and placenta percreta (7.7 %). Maternal deaths and perinatal deaths were 30.8 and 53.8 %, respectively. Sub-total hysterectomy was done in 8 cases and in 1 patient laparotomy with repair was performed., Conclusion: Ruptured uterus causes a high risk in patients. An unscarred uterus can undergo rupture even without etiological or risk factors. The patients with mismanaged labor, grand multiparas, and obstructed prolonged labor must be managed by properly trained personnel at a tertiary care center in order to avoid the morbidity or mortality., Competing Interests: Compliance with Ethical Standards Ethical clearance For this type of study, formal consent is not required. This article does not contain any studies with human participants performed by any of the authors. Conflict of interest Manisha Vernekar and Rajib Roy declare that they have no conflict of interest.

Progesterone is a physiologic regulator of sperm hyperactivation and acrosome reaction and it does so by activating a range of kinases present in the spermatozoa. In the present study, the involvement of the AKT- phosphatidylinositol 3-kinase (PI3K) signaling pathway in mediating progesterone response in human spermatozoa was investigated. In capacitated spermatozoa, progesterone transiently and concentration dependently lead to phosphorylation of AKT at both Thr 308 and Ser 473 in the tail region. This phosphorylation was inhibited by the PI3K inhibitor wortmannin, suggesting that progesterone leads to activation of PI3K-AKT pathway. The activation of AKT in response to progesterone is calcium dependent and the CatSper channel inhibitor mibefradil significantly reduced progesterone mediated AKT phosphorylation. Preincubation of spermatozoa with wortmannin inhibited the progesterone mediated increase in tyrosine phosphorylation and also attenuated the increase in number of motile, progressively motile and hyperactive spermatozoa but not the number of acrosome reacted spermatozoa. These observations imply that progesterone via CatSper activates the PI3K-AKT pathway required for motility and hyperactivation but not for acrosome reaction., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)