The BKCa (slo) channel regulates the cardiac function of Drosophila.

The large conductance, calcium, and voltage-active potassium channels (BKCa) were originally discovered in Drosophila melanogaster as slowpoke (slo). They are extensively characterized in fly models as ion channels for their roles in neurological and muscular function, as well as aging. BKCa is known to modulate cardiac rhythm and is localized to the mitochondria. Activation of mitochondrial BKCa causes cardioprotection from ischemia-reperfusion injury, possibly via modulating mitochondrial function in adult animal models. However, the role of BKCa in cardiac function is not well-characterized, partially due to its localization to the plasma membrane as well as intracellular membranes and the wide array of cells present in mammalian hearts. Here we demonstrate for the first time a direct role for BKCa in cardiac function and cardioprotection from IR injury using the Drosophila model system. We have also discovered that the BKCa channel plays a role in the functioning of aging hearts. Our study establishes the presence of BKCa in the fly heart and ascertains its role in aging heart function.

Chloride ions in health and disease.

Chloride is a key anion involved in cellular physiology by regulating its homeostasis and rheostatic processes. Changes in cellular Cl- concentration result in differential regulation of cellular functions such as transcription and translation, post-translation modifications, cell cycle and proliferation, cell volume, and pH levels. In intracellular compartments, Cl- modulates the function of lysosomes, mitochondria, endosomes, phagosomes, the nucleus, and the endoplasmic reticulum. In extracellular fluid (ECF), Cl- is present in blood/plasma and interstitial fluid compartments. A reduction in Cl- levels in ECF can result in cell volume contraction. Cl- is the key physiological anion and is a principal compensatory ion for the movement of the major cations such as Na+, K+, and Ca2+. Over the past 25 years, we have increased our understanding of cellular signaling mediated by Cl-, which has helped in understanding the molecular and metabolic changes observed in pathologies with altered Cl- levels. Here, we review the concentration of Cl- in various organs and cellular compartments, ion channels responsible for its transportation, and recent information on its physiological roles.

Intrauterine Administration of Autologous Platelet-Derived Growth Factor Concentrate (aka Autologous Blood Cell Derivative) Improves the Endometrial Thickness in 'Thin' Endometrium in the Frozen Embryo Transfer Cycle.

Context: Thin endometrium during the frozen embryo transfer cycles leads to cycle cancellation. The embryo transfer cycle getting deferred is an unpleasant experience for the patients and the fertility specialist. Aims: The purpose of this study is to evaluate the effectiveness of Autologous Blood Cell Derivative (ABCD) growth factor concentrate to obtain an optimal thickness of endometrium for embryo transfer during IVF treatments, where rapid regeneration is crucial for the expected therapeutic outcome. Settings and Design: A retrospective cohort study was conducted in Manipal Assisted Reproduction Center, a referral center in Southern India. Methods and Material: Fifty-six patients with thin endometrium were administered three doses of ABCD growth factor concentrate as per the protocol after informed consent. All of them had a history of embryo transfer (ET) cancellation in frozen-thawed embryo cycles due to inadequate growth of the endometrium despite therapy with estrogens and drugs for improving uterine blood circulation. Results: The endometrium thickness during the implantation window in the patients included in the study averaged 6.48 ± 1.19 mm. After the intervention, 55 out of 56 patients (98.2%) showed a considerable change in the thickness of the endometrium layer with an average thickness of 8.48 ± 1.32 mm (< 0.0001, SE 0.233, 95% CI 1.58-2.5). Out of the 55 patients, 20 got pregnant, i.e., 36.4% pregnancy rate. Till date, thirteen pregnancies had live births (65%), three pregnancies (15%) were biochemical pregnancies, 1 (5%) was ectopic, and three pregnancies (15%) had spontaneous miscarriage before eight weeks. When we compared the endometrial thickness (EMT) in the pregnant and non-pregnant groups pre- and post-ABCD instillation, (6.47 ± 1.31 mm vs 6.48 ± 1.4 mm, p = 0.98 and 8.68 ± 1.32 mm vs 8.48 ± 1.32 mm, p value 0.59) the p value was not statistically significant. Conclusions: The implantation, clinical pregnancy and live birth rates were 36.4, 30 and 65%, respectively. This result is a significant improvement for patients with thin endometrium for whom we would otherwise cancel the frozen transfer. An autologous resource is a safe, readily available and inexpensive treatment modality.

Biophysical characterization of chloride intracellular channel 6 (CLIC6).

Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293 cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293 cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10 µM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.

HIV Linkage to Care and Pre-Exposure Prophylaxis Among Persons in Non-Health Care Sites Who Are Tested for HIV for the First Time, United States, 2019.

CONTEXT: The Centers for Disease Control and Prevention recommends that all persons aged 13 to 64 years are tested for human immunodeficiency virus (HIV). However, results from US surveys show that 50% of persons and less had ever tested for HIV. PROGRAM: The Centers for Disease Control and Prevention annually funds 60 health departments to conduct comprehensive HIV prevention and surveillance activities that include HIV testing. IMPLEMENTATION: We selected the 31 health departments with quality data (ie, ≤20% missing or invalid values for variables to verify linkage to HIV medical care and new HIV diagnoses) in 2019. Main outcomes were new HIV diagnoses, linkage, and pre-exposure prophylaxis (PrEP) awareness and referrals. We used SAS 9.4 to conduct descriptive, chi-square, and multivariate regression analyses. Our objectives were to determine outcomes and characteristics of persons in non-health care settings who tested for HIV for the first time. EVALUATION: Compared with persons who previously tested for HIV, persons who tested for the first time were more likely to be aged 13 to 29 years than aged 30 years and older (62.0% [24 295/39 192] vs 42.1% [61 911/147 087], P < .001) and have a higher percentage of new HIV diagnoses (0.6% [242/39 320] vs 0.5% [667/147 475], P < .001). Among persons who tested for the first time, overall percentages of linkage, PrEP awareness, and PrEP referral were 73.4%, 33.3%, and 30.8%, respectively. Compared with referent groups, persons who tested for the first time in the South and had a new HIV diagnosis were less likely to be linked (adjusted prevalence ratio [aPR] = 0.72, 95% confidence interval [CI]: 0.59-0.89); persons who inject drugs were less likely to be aware of PrEP (aPR = 0.84, 95% CI: 0.77-0.91); and persons in the Northeast were less likely to receive PrEP referrals (aPR = 0.28, 95% CI: 0.26-0.31). DISCUSSION: Non-health care sites should consider increasing HIV testing, PrEP awareness, and prompt referrals to PrEP and HIV treatment services for persons who have never previously tested.

HIV Positivity, Linkage to Medical Care, Interview for Partner Services, and Pre-Exposure Prophylaxis Awareness and Referral Among Men Who Have Sex With Men Tested in Non-healthcare Settings in the United States, 2019.

OBJECTIVES: Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. This study reports data on HIV testing program outcomes among MSM tested for HIV in non-healthcare settings in the United States. METHODS: We analyzed Centers for Disease Control and Prevention's National HIV Prevention Program Monitoring and Evaluation data collected in 2019. Descriptive and multivariate robust Poisson regression analyses were conducted to summarize the patterns of HIV testing program outcomes [ie, positivity, linkage to HIV medical care within 30 days of diagnosis, interview for partner services (PS), and pre-exposure prophylaxis (PrEP) awareness and referral] by demographic characteristics, HIV prevalence, and testing site type. RESULTS: A total of 123,251 HIV tests were conducted among MSM; of these, 1773 (1.4%) were newly diagnosed with HIV. Among MSM newly diagnosed with HIV, 75% were linked to HIV medical care and 80% were interviewed for PS. Among MSM who tested HIV-negative, 63% were aware of PrEP and 47% of those who were eligible for PrEP were referred to PrEP providers. Referral or linkage to services varied by demographic characteristics or other factors. CONCLUSIONS: Linkage to HIV medical care and interview for PS among MSM newly diagnosed with HIV in non-healthcare settings were below national or funding program targets. Most MSM with risk factors for HIV infection were not referred to PrEP providers. Expanded efforts to address barriers to equitable access to services may help improve HIV-related outcomes among MSM and contribute to ending the HIV epidemic in the United States.

Crossing the Hurdle of a Low Oocyte Yield in an in vitro Fertilization Cycle to Obtain Mature Oocytes.

The complex process of oocyte maturation involves a coordinated set of events to take place so that an adequate number of oocytes can be obtained during an oocyte pickup procedure following controlled ovarian stimulation. A weak link in any of the steps can yield a sparse number of oocytes which can be a setback in the process.

Random Start Ovarian Stimulation.

Fertility preservation is emerging in recent years as an important option for various indications many of which being for cancer patients and for certain benign conditions as well. In the present case report, we set out to utilise the same protocol, however, for different indications.

Inhibition of BKCa channels protects neonatal hearts against myocardial ischemia and reperfusion injury.

BKCa channels are large-conductance calcium and voltage-activated potassium channels that are heterogeneously expressed in a wide array of cells. Activation of BKCa channels present in mitochondria of adult ventricular cardiomyocytes is implicated in cardioprotection against ischemia-reperfusion (IR) injury. However, the BKCa channel's activity has never been detected in the plasma membrane of adult ventricular cardiomyocytes. In this study, we report the presence of the BKCa channel in the plasma membrane and mitochondria of neonatal murine and rodent cardiomyocytes, which protects the heart on inhibition but not activation. Furthermore, K+ currents measured in neonatal cardiomyocyte (NCM) was sensitive to iberiotoxin (IbTx), suggesting the presence of BKCa channels in the plasma membrane. Neonatal hearts subjected to IR when post-conditioned with NS1619 during reoxygenation increased the myocardial infarction whereas IbTx reduced the infarct size. In agreement, isolated NCM also presented increased apoptosis on treatment with NS1619 during hypoxia and reoxygenation, whereas IbTx reduced TUNEL-positive cells. In NCMs, activation of BKCa channels increased the intracellular reactive oxygen species post HR injury. Electrophysiological characterization of NCMs indicated that NS1619 increased the beat period, field, and action potential duration, and decreased the conduction velocity and spike amplitude. In contrast, IbTx had no impact on the electrophysiological properties of NCMs. Taken together, our data established that inhibition of plasma membrane BKCa channels in the NCM protects neonatal heart/cardiomyocytes from IR injury. Furthermore, the functional disparity observed towards the cardioprotective activity of BKCa channels in adults compared to neonatal heart could be attributed to their differential localization.

Calcium Channels in the Heart: Disease States and Drugs.

Calcium ions are the major signaling ions in the cells. They regulate muscle contraction, neurotransmitter secretion, cell growth and migration, and the activity of several proteins including enzymes and ion channels and transporters. They participate in various signal transduction pathways, thereby regulating major physiological functions. Calcium ion entry into the cells is regulated by specific calcium channels and transporters. There are mainly six types of calcium channels, of which only two are prominent in the heart. In cardiac tissues, the two types of calcium channels are the L type and the T type. L-type channels are found in all cardiac cells and T-type are expressed in Purkinje cells, pacemaker and atrial cells. Both these types of channels contribute to atrioventricular conduction as well as pacemaker activity. Given the crucial role of calcium channels in the cardiac conduction system, mutations and dysfunctions of these channels are known to cause several diseases and disorders. Drugs targeting calcium channels hence are used in a wide variety of cardiac disorders including but not limited to hypertension, angina, and arrhythmias. This review summarizes the type of cardiac calcium channels, their function, and disorders caused by their mutations and dysfunctions. Finally, this review also focuses on the types of calcium channel blockers and their use in a variety of cardiac disorders.

Trends in Condomless Sex Among MSM Who Participated in CDC-Funded HIV Risk-Reduction Interventions in the United States, 2012-2017.

Consistent and correct use of condoms can reduce the risk for sexually transmitted diseases, including HIV/AIDS. Studies have reported that condomless sex among men who have sex with men (MSM) has steadily increased in recent years. We analyzed data reported by 51 health departments regarding 82 556 HIV-positive and HIV-negative MSM 13 years or older and participated in Centers for Disease Control and Prevention-funded behavioral risk-reduction intervention programs during 2012-2017. The percentages of condomless sex increased from 56.3% to 72.0% (estimated annual percent change [EAPC] = 7.1%) among HIV-positive MSM and from 46.0% to 70.5% (EAPC = 4.1%) among HIV-negative MSM. Continued increases in condomless sex might disrupt progress in ending the HIV/AIDS epidemic. Transmission risk associated with condomless sex can be reduced by ensuring that HIV-positive persons know their status early and are linked to care to achieve viral suppression and those at risk for acquiring HIV/AIDS can readily access preexposure prophylaxis.

Factors Associated With Partner Notification, Testing, and Positivity in HIV Partner Services Programs in the United States, 2013 to 2017.

BACKGROUND: Human immunodeficiency virus (HIV) partner services are an essential component of comprehensive HIV prevention and care. We examined factors associated with partner notification, HIV testing, and HIV positivity among partners of HIV-diagnosed persons (index persons) contacted by Centers for Disease Control and Prevention (CDC)-funded state and local health departments. METHODS: We analyzed partner service data submitted to the CDC by 61 state and local health departments from 2013 to 2017. Using multivariate Poisson regression-adjusted for clustering effects among partners reported by a common index person-we assessed associations between 3 outcomes of interest (partner notification, HIV testing, and HIV positivity) and the demographic characteristics, risk behaviors, geographic region, and service year of index persons and their partners. RESULTS: A total of 51,368 sexual and/or needle-sharing partners were matched with 33,524 index persons. Of notifiable partners, 97.2% were notified of their potential HIV exposure, and 52.3% were tested for HIV. Among 21,842 notified and tested partners, 23.8% were newly diagnosed with an HIV infection. Partner notification, HIV testing, and HIV positivity were associated with both partner and index person characteristics (individually and interactively), geographic region, and year of service. CONCLUSIONS: Partner service programs provided through CDC-funded health departments were effective in both partner notification and identification of undiagnosed HIV infection among partners. However, HIV testing rate among notified partners remained low. Implementing strategies to address gaps in HIV testing can contribute toward ending the HIV epidemic in the United States.

HIV Preexposure Prophylaxis Awareness and Referral to Providers Among Hispanic/Latino Persons - United States, 2019.

Hispanic or Latino* (Hispanic) persons are disproportionately affected by HIV in the United States. In 2019, Hispanic persons accounted for 18% of the U.S. population, but for 29% of new diagnoses of HIV infection (1). The Ending the HIV Epidemic in the U.S. (EHE) initiative aims to reduce new HIV infections by 90% by 2030 (2). Preexposure prophylaxis (PrEP), medication taken to prevent acquisition of HIV, is an effective strategy for preventing HIV infection.† To examine PrEP awareness and referral to providers among Hispanic persons, CDC analyzed 2019 National HIV Prevention Program Monitoring and Evaluation HIV testing data. Approximately one quarter (27%) of Hispanic persons tested for HIV at CDC-funded sites (n = 310,954) were aware of PrEP, and 22% of those who received a negative HIV test result and were eligible for referral (111,644) were referred to PrEP providers. PrEP awareness and referrals among Hispanic persons were lower compared with those among non-Hispanic White persons. Among Hispanic persons, significant differences were found in PrEP awareness and referrals by age, gender, race, population group, geographic region, and test setting. HIV testing programs can expand PrEP services for Hispanic persons by implementing culturally and linguistically appropriate strategies that routinize PrEP education and referral, collaborating with health care and other providers, and addressing social and structural barriers.

Tumor-Induced Cardiac Dysfunction: A Potential Role of ROS.

Cancer and heart diseases are the two leading causes of mortality and morbidity worldwide. Many cancer patients undergo heart-related complications resulting in high incidences of mortality. It is generally hypothesized that cardiac dysfunction in cancer patients occurs due to cardiotoxicity induced by therapeutic agents, used to treat cancers and/or cancer-induced cachexia. However, it is not known if localized tumors or unregulated cell growth systemically affect heart function before treatment, and/or prior to the onset of cachexia, hence, making the heart vulnerable to structural or functional abnormalities in later stages of the disease. We incorporated complementary mouse and Drosophila models to establish if tumor induction indeed causes cardiac defects even before intervention with chemotherapy or onset of cachexia. We focused on one of the key pathways involved in irregular cell growth, the Hippo-Yorkie (Yki), pathway. We used overexpression of the transcriptional co-activator of the Yki signaling pathway to induce cellular overgrowth, and show that Yki overexpression in the eye tissue of Drosophila results in compromised cardiac function. We rescue these cardiac phenotypes using antioxidant treatment, with which we conclude that the Yki induced tumorigenesis causes a systemic increase in ROS affecting cardiac function. Our results show that systemic cardiac dysfunction occurs due to abnormal cellular overgrowth or cancer elsewhere in the body; identification of specific cardiac defects associated with oncogenic pathways can facilitate the possible early diagnosis of cardiac dysfunction.

Brief Report: HIV Testing, Diagnosis of HIV Infection, Linkage to Medical Care, and Interview for Partner Services Among Transgender Persons-United States, 2012-2017.

BACKGROUND: Transgender persons are at high risk for HIV infection. Testing is a key component of the national effort to end the HIV epidemic in the United States. SETTING: Sixty-one local and state health departments and 150 community-based organizations funded by the Centers for Disease Control and Prevention to conduct HIV testing programs. METHODS: We analyzed HIV testing data submitted to the Centers for Disease Control and Prevention by funded health departments and community-based organizations during 2012-2017. Descriptive analysis examined patterns of HIV testing and key outcomes (diagnosis of HIV infection, linkage to HIV medical care, and interview for partner services) among transgender persons. Multivariate robust Poisson regression was used to assess associations between HIV testing outcomes and demographic characteristics, census region, and test setting. RESULTS: A total of 82,818 HIV tests were provided to transgender persons. Of these, 2280 (2.8%) transgender persons were diagnosed with HIV infection; 1556 (1.9%) received a new and 724 (0.9%) a previous diagnosis with HIV infection. The highest percentage of new HIV diagnosis was found among persons tested in correctional settings (4.6%), non-Hispanic Blacks (3.5%) and transgender women (2.4%). Among newly diagnosed persons, 85.0% were linked to HIV medical care ≤90 days after diagnosis and 63.5% were interviewed for partner services. CONCLUSIONS: HIV positivity was high, and the delivery of partner services was low, among transgender persons. HIV testing outcomes among transgender persons varied significantly by demographic characteristics and test setting. HIV prevention programs that are responsive to the needs of transgender persons may address gender-related disparities in HIV testing outcomes.

Postcode based participatory disease surveillance systems : a comparison with traditional risk-based surveillance and its application in the COVID-19 pandemic.

BACKGROUND: Background: The SARS-Cov-2 infection has rapidly saturated health systems and traditional surveillance networks are finding hard to keep pace with its spread. We designed a participatory disease surveillance (PDS) system, to capture symptoms of Influenza-like illness (ILI) to estimate SARS-CoV-2 infection in the community. While data generated by these platforms can help public health organisations find community hotspots and effectively direct control measures, it has never been compared to traditional systems. OBJECTIVE: Methods and Objectives: A completely anonymised web based PDS system, www.trackcovid-19.org was developed. We evaluated the symptomatic responses received form the PDS system to the traditional risk based surveillance carried out by the Bruhat Bengaluru Mahanagara Palike over a period of 45 days in the South Indian city of Bengaluru. METHODS: Methods and Objectives: A completely anonymised web based PDS system, www.trackcovid-19.org was developed. We evaluated the symptomatic responses received form the PDS system to the traditional risk based surveillance carried out by the Bruhat Bengaluru Mahanagara Palike over a period of 45 days in the South Indian city of Bengaluru. RESULTS: Results: The PDS system recorded 11062 entries from 106 Postal codes. A healthy response was obtained from 10863 users while 199 (1.8%) reported symptomatic. Subgroup analysis of a 14 day symptomatic window recorded 33 (0.29%) responses. Risk based surveillance was carried out covering a population of 605,284 with 209 (0.03%) individuals identified symptomatic. CONCLUSIONS: Conclusion: Web PDS platforms provide better visualisation of community infection when compared to traditional risk based surveillance systems. They are extremely useful by providing real time information in the extended battle against this pandemic. When integrated into national disease surveillance systems, they can provide long term community surveillance adding an important cost-effective layer to already available data sources.

Human Immunodeficiency Virus Testing, Diagnosis, Linkage to Care, and Prevention Services Among Persons Who Inject Drugs, United States, 2012-2017.

BACKGROUND: Human immunodeficiency virus (HIV) testing and early diagnosis is associated with effective disease management and reduction in HIV transmission among persons who inject drugs (PWID). We examined trends in HIV testing outcomes among PWID during 2012-2017. METHODS: Centers for Disease Control and Prevention (CDC)-funded HIV testing data submitted by 61 health departments and 150 directly-funded community-based organizations during 2012-2017 were analyzed. We calculated estimated annual percentage changes (EAPC) to assess trends for HIV testing and testing outcomes. RESULTS: A total of 19 739 857 CDC-funded HIV tests were conducted during 2012-2017. Of these, 529 349 (2.7%) were among PWID. The percentage of newly diagnosed HIV increased from .7% in 2012 to .8% in 2017 (EAPC, 4.15%). The percentage interviewed for partner services increased from 46.7% in 2012 to 66.3% in 2017 (EAPC, 1.81%). No significant change was identified in trends for linkage to HIV medical care ≤90 days after diagnosis (EAPC, 0.52%) or referral to HIV prevention services (EAPC, 0.98%). CONCLUSIONS: Human immunodeficiency virus testing data revealed an increasing trend in newly diagnosed HIV among PWID but not linkage to HIV medical care or referral to prevention services. Expanding efforts to increase HIV testing and enhance linkage to services can lead to reductions in HIV transmission and improved health outcomes.

Intracellular Chloride Channels: Novel Biomarkers in Diseases.

Ion channels are integral membrane proteins present on the plasma membrane as well as intracellular membranes. In the human genome, there are more than 400 known genes encoding ion channel proteins. Ion channels are known to regulate several cellular, organellar, and physiological processes. Any mutation or disruption in their function can result in pathological disorders, both common or rare. Ion channels present on the plasma membrane are widely acknowledged for their role in various biological processes, but in recent years, several studies have pointed out the importance of ion channels located in intracellular organelles. However, ion channels located in intracellular organelles are not well-understood in the context of physiological conditions, such as the generation of cellular excitability and ionic homeostasis. Due to the lack of information regarding their molecular identity and technical limitations of studying them, intracellular organelle ion channels have thus far been overlooked as potential therapeutic targets. In this review, we focus on a novel class of intracellular organelle ion channels, Chloride Intracellular Ion Channels (CLICs), mainly documented for their role in cardiovascular, neurophysiology, and tumor biology. CLICs have a single transmembrane domain, and in cells, they exist in cytosolic as well as membranous forms. They are predominantly present in intracellular organelles and have recently been shown to be localized to cardiomyocyte mitochondria as well as exosomes. In fact, a member of this family, CLIC5, is the first mitochondrial chloride channel to be identified on the molecular level in the inner mitochondrial membrane, while another member, CLIC4, is located predominantly in the outer mitochondrial membrane. In this review, we discuss this unique class of intracellular chloride channels, their role in pathologies, such as cardiovascular, cancer, and neurodegenerative diseases, and the recent developments concerning their usage as theraputic targets.

Human Cardiac Progenitor Cells Enhance Exosome Release and Promote Angiogenesis Under Physoxia.

Studies on cardiac progenitor cells (CPCs) and their derived exosomes therapeutic potential have demonstrated only modest improvements in cardiac function. Therefore, there is an unmet need to improve the therapeutic efficacy of CPCs and their exosomes to attain clinically relevant improvement in cardiac function. The hypothesis of this project is to assess the therapeutic potential of exosomes derived from human CPCs (hCPCs) cultured under normoxia (21% O2), physoxia (5% O2) and hypoxia (1% O2) conditions. hCPCs were characterized by immunostaining of CPC-specific markers (NKX-2.5, GATA-4, and c-kit). Cell proliferation and cell death assay was not altered under physoxia. A gene expression qPCR array (84 genes) was performed to assess the modulation of hypoxic genes under three different oxygen conditions as mentioned above. Our results demonstrated that very few hypoxia-related genes were modulated under physoxia (5 genes upregulated, 4 genes down regulated). However, several genes were modulated under hypoxia (23 genes upregulated, 9 genes downregulated). Furthermore, nanoparticle tracking analysis of the exosomes isolated from hCPCs under physoxia had a 1.6-fold increase in exosome yield when compared to normoxia and hypoxia conditions. Furthermore, tube formation assay for angiogenesis indicated that exosomes derived from hCPCs cultured under physoxia significantly increased tube formation as compared to no-exosome control, 21% O2, and 1% O2 groups. Overall, our study demonstrated the therapeutic potential of physoxic oxygen microenvironment cultured hCPCs and their derived exosomes for myocardial repair.