Peptide-Guided Nanoparticle Drug Delivery for Cardiomyocytes.

BACKGROUND: Nanoparticles (NPs) have been extensively utilized as a drug delivery system to control the release of therapeutic agents to treat cardiac injuries. However, despite the advantages of utilizing NP-based drug delivery for treating heart diseases, the current delivery system lacks specificity in targeting the cardiac tissue, thus limiting its application. METHODS: We created three linear peptides, each consisting of 16-24 amino acids. These peptides were conjugated on the surface of NPs, resulting in the formation of cardiac targeting peptide (CTP)-NPs (designated as CTP-NP1, CTP-NP2, and CTP-NP3). To assess their effectiveness, we compared the binding efficiency of these three CTP-NPs to human and mouse cardiomyocytes. Additionally, we determined their distribution 24 h after injecting the CTP-NPs intravenously into adult C57BL/6J mice. RESULTS: When compared to control NPs without CTP (Con-NPs), all three CTP-NPs exhibited significantly increased binding affinity to both human and mouse cardiomyocytes in vitro and enhanced retention in mouse hearts in vivo. A thorough assessment of the heart sections demonstrated that the binding specificity of CTP-NP3 to cardiomyocytes in vivo was significantly greater than that of Con-NPs. None of the three CTP-NPs were proven to cause cardiomyocyte apoptosis. CONCLUSIONS: Biocompatible and safe CTP-NP3 can target the heart via binding to cardiomyocytes. This approach of targeting specific molecules-coated NPs may help in delivering therapeutic compounds to cardiomyocytes for the treatment of heart diseases with high efficacy and low toxicity to other tissues.

Newcastle disease burden in Nepal and efficacy of Tablet I2 vaccine in commercial and backyard poultry production.

Poultry (Gallus domesticus) farming plays an important role as an income generating enterprise in a developing country like Nepal, contributing more than 4% to the national Gross Domestic Product (GDP). Newcastle Disease (ND) is a major poultry disease affecting both commercial and backyard poultry production worldwide. There were more than 90 reported ND outbreaks in Nepal in 2018 with over 74,986 birds being affected. ND is responsible for over 7% of total poultry mortality in the country. Recent outbreaks of ND in 2021 affected many farms throughout Nepal and caused massive loss in poultry production. ND is caused by a single-stranded ribonucleic acid (RNA) virus that presents very similar clinical symptoms as Influenza A (commonly known as bird flu) adding much complexity to clinical disease identification and intervention. We conducted a nationwide ND and Influenza A (IA) prevalence study, collecting samples from representative commercial and backyard poultry farms from across the major poultry production hubs of Nepal. We used both serological and molecular assessments to determine disease exposure history and identification of strains of ND Virus (NDV). Of the 40 commercial farms tested, both NDV (n = 28, 70%) and IAV (n = 11, 27.5%) antibodies were detected in majority of the samples. In the backyard farms (n = 36), sero-prevalence of NDV and IAV were 17.5% (n = 7) and 7.5% (n = 3) respectively. Genotype II NDV was present in most of the commercial farms, which was likely due to live vaccine usage. We detected never reported Genotype I NDV in two backyard farm samples. Our investigation into 2021 ND outbreak implicated Genotype VII.2 NDV strain as the causative pathogen. Additionally, we developed a Tablet formulation of the thermostable I2-NDV vaccine (Ranigoldunga™) and assessed its efficacy on various (mixed) breeds of chicken (Gallus domesticus). Ranigoldunga™ demonstrated an overall efficacy >85% with a stability of 30 days at room temperature (25°C). The intraocularly administered vaccine was highly effective in preventing ND, including Genotype VII.2 NDV strain.

Biowaste-Derived, Highly Efficient, Reusable Carbon Nanospheres for Speedy Removal of Organic Dyes from Aqueous Solutions.

The current work explores the adsorptive efficiency of carbon nanospheres (CNSs) derived from oil palm leaves (OPL) that are a source of biowaste. CNSs were synthesized at 400, 600, 800 and 1000 °C, and those obtained at 1000 °C demonstrated maximum removal efficiency of ~91% for malachite green (MG). Physicochemical and microscopic characteristics were analysed by FESEM, TEM, FTIR, Raman, TGA and XPS studies. The presence of surface oxygen sites and the porosity of CNSs synergistically influenced the speed of removal of MG, brilliant green (BG) and Congo red (CR) dyes. With a minimal adsorbent dosage (1 mg) and minimum contact time (10 min), and under different pH conditions, adsorption was efficient and cost-effective (nearly 99, 91 and 88% for BG, MG and CR, respectively). The maximum adsorption capacities of OPL-based CNSs for BG were 500 and 104.16 mg/g for MG and 25.77 mg/g for CR. Adsorption isotherms (Freundlich, Langmuir and Temkin) and kinetics models (pseudo-first-order, pseudo-second-order and Elovich) for the adsorption processes of all three dyes on the CNSs were explored in detail. BG and CR adsorption the Freundlich isotherm best, while MG showed a best fit to the Temkin model. Adsorption kinetics of all three dyes followed a pseudo-second-order model. A reusability study was conducted to evaluate the effectiveness of CNSs in removing the MG dye and showed ~92% efficiency even after several cycles. Highly efficient CNSs with surface oxygen groups and speedy removal of organic dyes within 10 min by CNSs are highlighted in this paper.

Percutaneous-Reinforced Osteoplasty: A Review of Emerging Treatment Strategies for Bone Interventions.

Percutaneous-reinforced osteoplasty is currently being investigated as a possible therapeutic procedure for fracture stabilization in high-risk patients, primarily in patients with bone metastases or osteoporosis. For these patients, a percutaneous approach, if structurally sound, can provide a viable method for treating bone fractures without the physiologic stress of anesthesia and open surgery. However, the low strength of fixation is a common limitation that requires further refinement in scaffold design and selection of materials, and may potentially benefit from tissue-engineering-based regenerative approaches. Scaffolds that have tissue regenerative properties and low inflammatory response promote rapid healing at the fracture site and are ideal for percutaneous applications. On the other hand, preclinical mechanical tests of fracture-repaired specimens provide key information on restoration strength and long-term stability and enable further design optimization. This review presents an overview of percutaneous-reinforced osteoplasty, emerging treatment strategies for bone repair, and basic concepts of in vitro mechanical characterization.

Identification of metabolic pathways underlying FGF1 and CHIR99021-mediated cardioprotection.

Acute myocardial infarction is a leading cause of death worldwide. We have previously identified two cardioprotective molecules - FGF1 and CHIR99021- that confer cardioprotection in mouse and pig models of acute myocardial infarction. Here, we aimed to determine if improved myocardial metabolism contributes to this cardioprotection. Nanofibers loaded with FGF1 and CHIR99021 were intramyocardially injected to ischemic myocardium of adult mice immediately following surgically induced myocardial infarction. Animals were euthanized 3 and 7 days later. Our data suggested that FGF1/CHIR99021 nanofibers enhanced the heart's capacity to utilize glycolysis as an energy source and reduced the accumulation of branched-chain amino acids in ischemic myocardium. The impact of FGF1/CHIR99021 on metabolism was more obvious in the first three days post myocardial infarction. Taken together, these findings suggest that FGF1/CHIR99021 protects the heart against ischemic injury via improving myocardial metabolism which may be exploited for treatment of acute myocardial infarction in humans.

Genetic insight into Birt-Hogg-Dubé syndrome in Indian patients reveals novel mutations at FLCN.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma (chromophobe). Here, we comprehensively studied the mutational background of 31 clinically diagnosed BHDS patients and their 74 asymptomatic related members from 15 Indian families. RESULTS: Targeted amplicon next-generation sequencing (NGS) and Sanger sequencing of FLCN in patients and asymptomatic members revealed a total of 76 variants. Among these variants, six different types of pathogenic FLCN mutations were detected in 26 patients and some asymptomatic family members. Two of the variants were novel mutations: an 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and a splice acceptor mutation (c.1301-1G > A). Two variants were Clinvar reported pathogenic mutations: a stop-gain (c.634C > T) and a 4-nucleotide duplication (c.1329_1332dupAGCC). Two known variants were: hotspot deletion (c.1285delC) and a splice donor mutation (c.1300 + 1G > A). FLCN mutations could not be detected in patients and asymptomatic members from 5 families. All these mutations greatly affected the protein stability and FLCN-FNIP2 interaction as observed by molecular docking method. Family-based association study inferred pathogenic FLCN mutations are significantly associated with BHDS. CONCLUSION: Six pathogenic FLCN mutations were detected in patients from 10 families out of 15 families in the cohort. Therefore, genetic screening is necessary to validate the clinical diagnosis. The pathogenic mutations at FLCN affects the protein-protein interaction, which plays key roles in various metabolic pathways. Since, pathogenic mutations could not be detected in exonic regions of FLCN in 5 families, whole genome sequencing is necessary to detect all mutations at FLCN and/or any undescribed gene/s that may also be implicated in BHDS.

Xeroderma Pigmentosum-Associated Childhood Interstitial Lung Disease.

Chromosomal breakage syndromes are a group of genetic disorders that are ascribable to the autosomal recessive mode of inheritance. Xeroderma pigmentosum is one of the chromosomal breakage syndromes which is due to the involvement of deformity in the deoxyribonucleic acid's nucleotide excision repair. Xeroderma pigmentosum is a genetic disorder, which is autosomal recessive, heterogeneous, and more common in cases of consanguinity, caused by mutations in at least 10 genes and 9 complementation groups. The disorder is very rare. Patients experience photophobia and extreme photosensitivity and have pigmentary changes in ultraviolet light-exposed areas of the body with freckling, premalignant, and malignant skin lesions arising in keratinocytes soon after the fleeting exposure to sunlight. Patients are also oversensitive to environmental mutagens such as cigarette smoke and possibly to the widely used agricultural insecticide, diazinon. Progressive neurological abnormalities along with some rare complications are also noticed among these patients. Symptoms and thoracic high-resolution computed tomography are considered for diagnosis. Only corticosteroids can be given to limit the progression of the disease. Xeroderma pigmentosum-related interstitial lung disease is one of the rarest forms and we thereby report an interesting case.

Optogenetic Control of Engrafted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Live Mice: A Proof-of-Concept Study.

Background: Cellular transplantation has emerged as promising approach for treating cardiac diseases. However, a poor engraftment rate limits our understanding on how transplanted cardiomyocytes contribute to cardiac function in the recipient's heart. Methods: The CRISPR/Cas9 technique was employed for stable and constitutive gene expression in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Myocardial infarction was induced in adult immunodeficient mice, followed by intramyocardial injection of hiPSC-CMs expressing either CCND2/channelrhodopsin 2 (hiPSC-CCND2OE/ChR2OECMs) or CCND2/luciferase (hiPSC-CCND2OE/LuciOECMs). Six months later, hemodynamics and intramural electrocardiogram were recorded upon blue light illuminations in anesthetized, open-chest mice. Results: Blue light resets automaticity of spontaneously beating hiPSC-CCND2OE/ChR2OECMs in culture, but not that of hiPSC-CCND2OE/LuciOECMs. Response to blue light was also observed in mice carrying large (>106 cells) intracardiac grafts of hiPSC-CCND2OE/ChR2OECM but not in mice carrying hiPSC-CCND2OE/LuciOECMs. The former exhibited single premature ventricular contractions upon light illumination or ventricular quadrigeminy upon second-long illuminations. At the onset of premature ventricular contractions, maximal systolic ventricular pressure decreased while ventricular volume rose concomitantly. Light-induced changes reversed upon resumption of sinus rhythm. Conclusions: We established an in vivo model for optogenetic-based modulation of the excitability of donor cardiomyocytes in a functional, reversible, and localized manner. This approach holds unique value for studying electromechanical coupling and molecular interactions between donor cardiomyocytes and recipient hearts in live animals.

Role of Inflammatory Niche and Adult Cardiomyocyte Coculture on Differentiation, Matrix Synthesis, and Secretome Release by Human Bone Marrow Mesenchymal Stem Cells.

Myocardial infarction (MI) causes cardiomyocyte death, provokes innate immune response, and initiates tissue remodeling. The intrinsic healing process is insufficient to replace the lost cells, or regenerate and restore the functional features of the native myocardium. Autologous bone marrow-derived mesenchymal stem cell (BM-MSC) transplantation is being explored to offer therapeutic potential after MI. Here, we cultured human BM-MSC spheroids in three-dimensional collagenous gels for 28 days under exposure to tumor necrosis factor-alpha (+ TNFα), and coculture with adult human cardiomyocytes, or with conditioned media (CM) pooled from TNFα-stimulated adult cardiomyocytes. MSC differentiation marker (CD90, GATA4, cTnI, cTnT, Cx43, MHC, α-actin) expression, matrix protein (elastin, hyaluonic acid, sulfated glycosaminoglycans, laminin, fibrillin, nitric oxide synthase) synthesis, and secretome (cytokines, chemokines, growth factors) release at days 12 and 28 were assessed. MSC density decreased with duration in all culture conditions, except in controls. GATA4 expression was higher in cocultures but lower in + TNFα cultures. Synthesis and deposition of various extracellular matrix proteins and lysyl oxidase within MSC cultures, as well as secretome composition, were strongly dependent on the culture condition and duration. Results suggest that TNFα-induced inflammation suppresses BM-MSC survival and differentiation into mature cardiomyocytes by day 28, while promoting matrix protein synthesis and cytokine release conducive to MI remodeling. These findings could have implications in developing tissue engienering and cell transplantation strategies targeting MI, as well as to develop therapuetics to target inflammation-induced matrix remodeling post-MI.

Sarcoidosis at the Pulmonary Medicine Department of a tertiary care hospital in Mumbai. Our experience and The New Modified Criteria Clinical Radiological Physiological (TNMC CRP) score for sarcoidosis: A novel proposition to assess the functional status.

Sarcoidosis is a multisystemic granulomatous disease most commonly involving the pulmonary system and having a myriad of manifestations. However literature is scanty pertaining to the profile and scoring system in sarcoidosis. This study was undertaken to understand the profile of sarcoidosis and an endeavor to assess the functional status with a simplified scoring system. This was an observational study undertaken in the department of Pulmonary Medicine at a tertiary care. The profile of these patients was studied in terms of clinical features, radiological findings, the New Modified Criteria Clinical Radiological Physiological (TNMC CRP) score, six-minute walk distance (6MWD), spirometry, arterial blood gas parameters, serum angiotensin converting enzyme (ACE) levels and tissue biopsy histopathology. The 68 patients included 41 women and 27 men with a mean age of 42.7 years. They comprised of 18 (27%), 39 (57%), 4 (6%), 7 (10%) cases of stage 1, 2, 3, 4 sarcoidosis respectively. Most common presenting symptom and sign was progressive dyspnea 49 (72%), and peripheral lymphadenopathy 15 (22%). Serum ACE was elevated in 57 (83%). The average 6MWD was 360 meters. Most common high resolution computed tomography (HRCT) finding was mediastinal lymphadenopathy and peri-bronchovascular nodules. Spirometry was restrictive abnormality in 48 (96%) patients. Evidence of pulmonary hypertension (PH) was present in 32 (47%) patients. Tissue diagnosis revealed granulomatous inflammation in 51 biopsies with a transbronchial lung biopsy (TBLB) yield of 62%. The average TNMC CRP score was 5. There was a positive correlation between this score and 6MWD which was statistically significant. The score correlated with the functional status. Diagnosis of sarcoidosis warrants a comprehensive and multimodality approach. HRCT and tissue biopsy are the most important diagnostic armamentariums. Modified simplified scores help assess the functional status of the disease.

Birt-Hogg-Dubé syndrome - an unique case series.

Birt-Hogg-Dubé syndrome (BHDS) is an uncommon autosomal dominant syndrome. It is also known as Hornstein-Knickenberg syndrome. It is an inherited disorder culminating in mutations in folliculin coding gene (FLCN). The clinical exhibitions of the syn-drome are multi-systemic, comprising of a constellation of pulmonary, dermatologic and renal system manifestations. The most common presentations include fibrofolliculomas, renal cell carcinomas, lung cysts and spontaneous pneumothorax. The treatment is conservative with regular monitoring of the renal and lung parameters. Fibrofolliculomas may require surgical excision and recurrent events of pneumothorax may warrant pleurodesis. We reported a case series of 2 patients presenting with symptoms of progressive breathlessness along with dermatological manifestations and subsequently showing radiological manifestations of Birt-Hogg-Dubé syndrome in the form of lung cysts.

Prevalence and profile of sleep-disordered breathing and obstructive sleep apnea in patients with interstitial lung disease at the pulmonary medicine department of a tertiary care hospital in Mumbai.

BACKGROUND: Sleep-disordered breathing (SDB), predominantly obstructive sleep apnea (OSA), is a frequent phenomenon in interstitial lung disease (ILD) and may be associated with significant morbidity and mortality. METHODOLOGY: A prospective, observational, hospital-based study was conducted in a tertiary care hospital after ethics committee permission. The study group consisted of 100 consecutive ILD patients diagnosed by a multidisciplinary diagnosis. They were evaluated for the prevalence of SDB with a polysomnography after a comprehensive history, detailed clinical examination, calculation of various pretest probability scores, and relevant prerequisite workup. RESULTS: Out of the total 100 ILD patients, 44 were male (44%) and 56 were female (56%). SDB was present in 57 (57%) patients. Of these, 29 (29%) were found to have only nocturnal oxygen desaturation (NOD), while 28 (28%) had OSA. The 28 cases of OSA were distributed as 15 mild OSA (53.57%), 10 moderate OSA (35.71%), and 3 severe OSA (10.71%). The patients were divided into the following four groups: total study Group (A), patients with OSA (Group B), patients with NOD without OSA (Group C), and no SDB (Group D). The mean forced vital capacity values predicted in the four groups were 53.67%, 50%, 45.56%, and 57.87%, respectively. The mean body mass index in the four groups was 24.56, 27, 26.98, and 24.89 kg/m2, respectively. The mean 6-min walk distance in the four groups was 280.7, 250, 256.65, and 311.4 m, respectively. The mean partial pressure of oxygen in the four groups was 65.65, 60, 62.10, and 75.66 mmHg, respectively. The mean apnea-hypopnea index in the study group was 2.98/h, 8.6/h with mild OSA, 21.69/h with moderate OSA, 48.78/h with severe OSA, 3.89/h in patients having NOD without OSA, and 2.54/h in patients with no SDB. CONCLUSION: SDB in ILD is associated with a significant impact on the cardinal determinants of functional capacity, lung function, and quality of life.

"Esophagomediastinal fistula presenting as drug resistant tuberculosis".

Esophageal tuberculosis is one of the rarest forms of tuberculosis with higher incidence in immunocompromised cases. In majority of cases it is seen associated with esophagomediastinal and esophagotracheal fistulas. Diagnosis is established with the help of esophagoscopy followed by histopathology and microbiological analysis of biopsy sample. Treatment with antituberculous therapy alone is sufficient in majority of cases, however surgical management is mandatory in severe and non resolving cases. We thereby report an interesting case of esophagomediastinal fistula presenting as drug resistant tuberculosis with retroviral disease.

Nanoparticle-Mediated Drug Delivery for Treatment of Ischemic Heart Disease.

The regenerative capacity of an adult cardiac tissue is insufficient to repair the massive loss of heart tissue, particularly cardiomyocytes (CMs), following ischemia or other catastrophic myocardial injuries. The delivery methods of therapeutics agents, such as small molecules, growth factors, exosomes, cells, and engineered tissues have significantly advanced in medical science. Furthermore, with the controlled release characteristics, nanoparticle (NP) systems carrying drugs are promising in enhancing the cardioprotective potential of drugs in patients with cardiac ischemic events. NPs can provide sustained exposure precisely to the infarcted heart via direct intramyocardial injection or intravenous injection with active targets. In this review, we present the recent advances and challenges of different types of NPs loaded with agents for the repair of myocardial infarcted heart tissue.

Management of interstitial lung diseases: A consensus statement of the Indian Chest Society (ICS) and National College of Chest Physicians (NCCP).

BACKGROUND: Interstitial lung disease (ILD) is a complex and heterogeneous group of acute and chronic lung diseases of several known and unknown causes. While clinical practice guidelines (CPG) for idiopathic pulmonary fibrosis (IPF) have been recently updated, CPG for ILD other than IPF are needed. METHODS: A working group of multidisciplinary clinicians familiar with clinical management of ILD (pulmonologists, radiologist, pathologist, and rheumatologist) and three epidemiologists selected by the leaderships of Indian Chest Society and National College of Chest Physicians, India, posed questions to address the clinically relevant situation. A systematic search was performed on PubMed, Embase, and Cochrane databases. A modified GRADE approach was used to grade the evidence. The working group discussed the evidence and reached a consensus of opinions for each question following face-to-face discussions. RESULTS: Statements have been made for each specific question and the grade of evidence has been provided after performing a systematic review of literature. For most of the questions addressed, the available evidence was insufficient and of low to very low quality. The consensus of the opinions of the working group has been presented as statements for the questions and not as an evidence-based CPG for the management of ILD. CONCLUSION: This document provides the guidelines made by consensus of opinions among experts following discussion of systematic review of evidence pertaining to the specific questions for management of ILD other than IPF. It is hoped that this document will help the clinician understand the accumulated evidence and help better management of idiopathic and nonidiopathic interstitial pneumonias.

Role of GeneXpert in the diagnosis of mycobacterium tuberculosis.

INTRODUCTION: GeneXpert (GX) is a novel, integrated, cartridge-based, nucleic acid amplification test with an established role for rapid diagnosis of Mycobacterium tuberculosis and detection of rifampicin resistance. AIM: To evaluate the role of GX in pulmonary and extrapulmonary tuberculosis (TB) cases. MATERIAL AND METHODS: A prospective study was conducted in the pulmonary medicine department of a tertiary care hospital after the Ethics Comittee permission. Data of 257 presumptive TB patients was retrieved for GX, acid fast bacilli smear and cul-ture (AFB smear and culture) and drug susceptibility test (DST). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of GX in diagnosis and determination of rifampicin resistance in pulmonary and extrapulmonary TB cases were calculated and compared with culture and DST results. RESULTS: Our study included 132 pulmonary and 125 extrapulmonary cases. On the basis of clinicoradiological and microbiological correlation, diagnosis of TB was confirmed in 104 pulmonary and 103 extrapulmonary cases. Out of a total of 104 pulmonary TB cases, 73 were rifampicin-sensitive and 31 were rifampicin-resistant cases. 103 extrapulmonary TB patients included 66 rifampicin-sensitive and 37 rifampicin-resistant cases. The sensitivity, specificity, PPV, NPV of GX in diagnosis and detection of rifampicin resistance in pulmonary TB was 95%, 93%, 98%, 84% and 96%, 100%, 100%, 96%, respectively. The sensitivity, specificity, PPV, NPV of GX in diagnosis and detection of rifampicin resistance in extrapulmonary TB cases was 79%, 86%, 96%, 47% and 97%, 95%, 97%, 95%, respectively. CONCLUSIONS: GX results are superior to smear microscopy and comparable to culture with shorter turnaround time.We recom-mend using it in routine TB diagnosis as this will expedite the management of patients with presumptive TB.

Tuberculosis in 2019.

Tuberculosis (TB) updates and guidelines have been published rapidly in last few years. The WHO and RNTCP have recommended suggestions that have changed the diagnostics and therapeutics paradigm in 2019. The rapid nature of these changes need to be appraised at the pulmonologist end. We conducted a google survey to study these gaps and subsequently review TB in 2019 focusing on the gaps in the survey. We narrate a short review covering the important diagnostic and therapeutic aspects in brief. We discuss the results of our google survey to address the knowledge gaps. Diagnosis, principles and rationale of therapy and treatment of drug sensitive and drug resistant tuberculosis including the shorter regimen and regrouping of drugs are important considerations of our review.

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair.

The paracrine effect, mediated by chemical signals that induce a physiological response on neighboring cells in the same tissue, is an important regenerative mechanism for stem cell-based therapy. Exosomes are cell-secreted nanovesicles (50-120 nm) of endosomal origin, and have been demonstrated to be a major contributor to the observed stem cell-mediated paracrine effect in the cardiac repair process. Following cardiac injury, exosomes deriving from exogenous stem cells have been shown to regulate cell apoptosis, proliferation, angiogenesis, and fibrosis in the infarcted heart. Exosomes also play a crucial role in the intercellular communication between donor and recipient cells. Human induced pluripotent stem cells (hiPSCs) are promising cell sources for autologous cell therapy in regenerative medicine. Here, we review recent advances in the field of progenitor-cell derived, exosome-based cardiac repair, with special emphasis on exosomes derived from hiPSCs.

Malignant Mesothelioma - Report of Two Cases with Different Presentations.

Malignant pleural mesothelioma (MPM) is a rare and aggressive neoplasm that stems from the mesothelial cells lining the visceral cavities, namely, the pleura, peritoneum, pericardium, and tunica vaginalis of the testes. MPM is the most common variant of these and constitutes up to 80% of all malignant mesotheliomas. It is usually associated with asbestos exposure and is a locally invasive neoplasm that spreads along pleura and can involve lungs with locoregional metastasis. Diagnosis remains challenging due to the latency between asbestos exposure and clinical presentation and the variable clinicoradiological manifestations. Meticulous history taking, high index of, suspicion and multimodality approach toward diagnosis are the keys to better prognosis. We hereby present two interesting cases of MPM with different presentations.

Alterations in phenotype and gene expression of adult human aneurysmal smooth muscle cells by exogenous nitric oxide.

Abdominal aortic aneurysms (AAA) are characterized by matrix remodeling, elastin degradation, absence of nitric oxide (NO) signaling, and inflammation, influencing smooth muscle cell (SMC) phenotype and gene expression. Little is known about the biomolecular release and intrinsic biomechanics of human AAA-SMCs. NO delivery could be an attractive therapeutic strategy to restore lost functionality of AAA-SMCs by inhibiting inflammation and cell stiffening. We aim to establish the differences in phenotype and gene expression of adult human AAA-SMCs from healthy SMCs. Based on our previous study which showed benefits of optimal NO dosage delivered via S-Nitrosoglutathione (GSNO) to healthy aortic SMCs, we tested whether such benefits would occur in AAA-SMCs. The mRNA expression of three genes involved in matrix degradation (ACE, ADAMTS5 and ADAMTS8) was significantly downregulated in AAA-SMCs. Total protein and glycosaminoglycans synthesis were higher in AAA-SMCs than healthy-SMCs (p < 0.05 for AAA-vs. healthy- SMC cultures) and was enhanced by GSNO and 3D cultures (p < 0.05 for 3D vs. 2D cultures; p < 0.05 for GSNO vs. non-GSNO cases). Elastin gene expression, synthesis and deposition, desmosine crosslinker levels, and lysyl oxidase (LOX) functional activity were lower, while cell proliferation, iNOS, LOX and fibrillin-1 gene expressions were higher in AAA-SMCs (p < 0.05 between respective cases), with differential benefits from GSNO exposure. GSNO and 3D cultures reduced MMPs -2, -9, and increased TIMP-1 release in AAA-SMC cultures (p < 0.05 for GSNO vs. non-GSNO cultures). AAA-SMCs were inherently stiffer and had smoother surface than healthy SMCs (p < 0.01 in both cases), but GSNO reduced stiffness (~25%; p < 0.01) and increased roughness (p < 0.05) of both cell types. In conclusion, exogenously-delivered NO offers an attractive strategy by providing therapeutic benefits to AAA-SMCs.