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Burn has terrible consequences for the affected patients, making them vulnerable to wound infections and septicemia, which results in physical and mental disability and death, necessitating superior treatment options. Human amniotic membrane (HAM) has been utilized in burn wounds for decades for its low immunogenicity, angiogenic, anti-inflammatory, and antimicrobial properties and for promoting epithelialization. Silver nanoparticles (AgNPs), on the other hand, have antimicrobial properties and promote fibroblast migration. This study aimed to determine the burn wound healing potential of HAM + AgNPs. The gel was prepared using HAM (1% and 2%), AgNPs, carbopol 934, acrylic acid, glycerine, and triethanolamine, and different physical properties (pH, water absorption, swelling variation, spreadability, etc.) of the gel were determined; nuclear magnetic resonance (NMR) spectroscopy, antibacterial activity, brine shrimp lethality test, and histopathological observation were conducted. In vivo studies with Wistar rats demonstrated better healing capabilities than individual components of the gel. Wound contraction percentage after 20 days was 96.1 ± 0.27% which was highly significant ( p  < 0.0001), and the epithelialization period was 23.67 ± 2.05 days ( p  < 0.01) for HAM + AgNPs which was preferable to the positive control, AgNPs, HAM, and negative control; also, the histopathologic observation using hematoxylin and eosin, and Masson's trichrome staining were showed the better healing progress for HAM + AgNPs. Both HAM and AgNPs had antibacterial activities against gram-positive and gram-negative bacteria. These results indicated that the formulated HAM + AgNPs gel had remarkable effectiveness in burn wound healing compared to others. Further studies will be conducted to determine the molecular mechanism behind wound healing., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Israt Jahan Jhumi et al.)

The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Akhtar, Basher, Nizam, Kamruzzaman, Khaton, Banna, Kaisar, Karmakar, Hakim, Akter, Ahmed, Tauheed, Islam, Ahmmed, Mahamud, Hasnat, Sumon, Rashed, Ghosh, Calderwood, Harris, Charles, LaRocque, Ryan, Banu, Shirin, Chowdhury, Bhuiyan and Qadri.)

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM + (both OX40 + CD137 + and OX40 + CD40L + ) CD4 + T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8 + AIMs (CD137 + CD69 + ), which indicates the exhaustion of CD8 + T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4 + T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2., Competing Interests: AS is a consultant for Gritstone Bio, Flow Pharma, ImmunoScape, Avalia, Moderna, Fortress, Repertoire, erson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. La Jolla Institute has filed for patent protection for various aspects of T cell epitope and vaccine design work. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bhuiyan, Al Banna, Kaisar, Karmakar, Hakim, Akter, Ahmed, Tauheed, Islam, Hasnat, Sumon, Rashed, Ghosh, Clemens, Banu, Shirin, Weiskopf, Sette, Chowdhury and Qadri.)

Exposure to bisphenol A (BPA) in the gestational period damages the reproductive health of offspring; detailed evidence regarding BPA-induced damage in testicular germ cells of offspring is still limited. In this study, pregnant mice (F0) were gavaged with three BPA doses (50 μg, 5 mg, and 50 mg/kg body weight (bw)/day; tolerable daily intake (TDI), no-observed-adverse-effect-level (NOAEL), and lowest-observed-adverse-effect level (LOAEL), respectively) on embryonic days 7 to 14, followed by investigation of the transgenerational effects of such exposure in male offspring. We observed that the NOAEL- and LOAEL-exposed F1 offspring had abnormalities in anogenital distance, nipple retention, and pubertal onset (days), together with differences in seminiferous epithelial stages and testis morphology. These effects were eradicated in the next F2 and F3 generations. Moreover, there was an alteration in the ratio of germ cell population and the apoptosis rate in germ cells increased in F1 offspring at the LOAEL dose. However, the total number of spermatogonia remained unchanged. Finally, a reduction in the stemness properties of spermatogonial stem cells in F1 offspring was observed upon LOAEL exposure. Therefore, we provide evidence of BPA-induced disruption of physiology and functions in male germ cells during the gestational period. This may lead to several reproductive health issues and infertility in offspring.

Bisphenol-A (BPA) exposure in an adult male can affect the reproductive system, which may also adversely affect the next generation. However, there is a lack of comprehensive data on the BPA-induced disruption of the association and functional characteristics of the testicular germ cells, which the present study sought to investigate. Adult male mice were administered BPA doses by gavage for six consecutive weeks and allowed to breed, producing generations F1-F4. Testis samples from each generation were evaluated for several parameters, including abnormal structure, alterations in germ cell proportions, apoptosis, and loss of functional properties of spermatogonial stem cells (SSCs). We observed that at the lowest-observed-adverse-effect level (LOAEL) dose, the testicular abnormalities and alterations in seminiferous epithelium staging persisted in F0-F2 generations, although a reduced total spermatogonia count was found only in F0. However, abnormalities in the proportions of germ cells were observed until F2. Exposure of the male mice (F0) to BPA alters the morphology of the testis along with the association of germ cells and stemness properties of SSCs, with the effects persisting up to F2. Therefore, we conclude that BPA induces physiological and functional disruption in male germ cells, which may lead to reproductive health issues in the next generation.

Many of the testicular cancer-survived patients, treated with chemotherapeutic drugs, show infertility, pre and postimplantation loss, and germ cell abnormality. Studies examining the negative effects of chemotherapeutic drugs on testicular germ cells are ongoing; however, information on the stemness properties and proteomic profiles of these cells are lacking. This study investigated the effects of chemotherapeutic drugs etoposide, cisplatin, bleomycin, and their combination (BEP) on the physiology and stem cell activity of mouse germ cells in vitro. Our results showed that treatment with the abovementioned drugs affected germ cell viability and decreased the number of proliferating germ cells significantly at specific concentrations (0.05 µM etoposide, 1 µM cisplatin, 10 µM bleomycin, and 0.1 µM BEP), which maintained a survival rate of >90%. We also observed a significantly higher percentage of apoptotic cells and alterations in the expression of undifferentiated and differentiated spermatogonia-related genes and marker proteins in germ cells exposed to abovementioned concentrations of the drugs. Next, we performed germ cell transplantation into recipient mice and observed a remarkable reduction in stemness properties of spermatogonial stem cells at these concentrations. Based on these results, we assessed the levels of differentially expressed proteins by performing proteomic analysis. We found that treatment with the abovementioned drugs induced cell damage, oxidative stress, metabolic disruption, and immune deficiency which may promote tumor regeneration, cytotoxicity, infertility, and transgenerational cellular function transmission. Thus, this study provides information about the chemotherapy-induced recurrent destruction and thereby can lead possible changes in medication.

Studies regarding bisphenol A (BPA) exposure and male (in)fertility have conventionally focused on modifications in ejaculated spermatozoa function from exposed individuals. However, mammalian spermatozoa are incapable of fertilization prior to achieving capacitation, the penultimate step in maturation. Therefore, it is necessary to investigate BPA-induced changes in capacitated spermatozoa and assess the consequences on subsequent fertilization. Here, we demonstrate the effect of gestational BPA exposure (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on the functions, biochemical properties, and proteomic profiles of F1 capacitated spermatozoa from adult mice. The data showed that high concentrations of BPA inhibited motility, motion kinematics, and capacitation of spermatozoa, perhaps because of increased lipid peroxidation and protein tyrosine nitration, and decreased intracellular ATP levels and protein kinase-A activity in spermatozoa. We also found that BPA compromised the rates of fertilization and early embryonic development. Differentially expressed proteins identified between BPA-exposed and control groups play a critical role in energy metabolism, stress responses, and fertility. Protein function abnormalities were responsible for the development of several diseases according to bioinformatics analysis. On the basis of these results, gestational exposure to BPA may alter capacitated spermatozoa function and the proteomic profile, ultimately affecting their fertility potential.

The endocrine disruptor bisphenol A (BPA) is well known for its adverse effect on male fertility. Growing evidence suggests that BPA may interact with testicular germ cells and cause infertility as a result of its estrogenic activity. Objective of current in vitro study was to investigate the proliferation, survivability and stemness properties of mouse testicular germ cells exposed to BPA, and to evaluate possible expression of cellular proteome. Our results showed that germ cell viability and proliferation were not affected by low concentrations (0.01, 0.1, 1, and 10 µM) although significant reduction observed at 100 µM BPA. Germ cell self-renewal and differentiation related marker proteins expression found unchanged at those concentrations. When BPA-exposed germ cells were transplanted into recipient testes, we observed fewer colonies at higher concentrations (10 and 100 µM). Additionally, a significant frequency of recombination failure during meiosis was observed in 10 µM BPA-exposed germ cell transplanted recipient. Moreover, experiment on continuous BPA-exposed and 100 µM BPA-recovered germ cells suggested that spermatogonial stem cells are more potential to survive in adverse environment. Finally, scrutinizing differentially expressed cellular proteins resulted from our proteomic analysis, we conclude that BPA exposure might be associated with several health risks and infertility.

Spermatogonial stem cells (SSCs) are essential for spermatogenesis throughout the lifespan of the male. However, the rarity of SSCs has raised the need for an efficient selection method, but little is known about culture conditions that stimulate monkey SSC proliferation in vitro . In this study, we report the development of effective enrichment techniques and in vitro culturing of germ cells from pre-pubertal monkey testes. Testis cells were analyzed by fluorescence-activated cell sorting techniques and were transplanted into the testes of nude mice to characterize SSCs. Thy-1-positive cells showed a higher number of colonies than the unselected control after xenotransplantation. Extensive colonization of monkey cells in the mouse testes indicated the presence of highly enriched populations of SSCs in the Thy-1-positive sorted cells. Furthermore, monkey testis cells were enriched by differential plating using extracellular matrix, laminin, and gelatin, and then cultured under various conditions. Isolation of monkey testicular germ cells by differential plating increased germ cell purity by 2.7-fold, following the combinational isolation method using gelatin and laminin. These enriched germ cells actively proliferated under culture conditions involving StemPro medium supplemented with bFGF, GDNF, LIF, and EGF at 37 °C. These results suggest that the enrichment and in vitro culture method proposed in the present study for harvesting a large number of functionally active monkey SSCs can be applied as the basis for efficient in vitro expansion of human SSCs., Competing Interests: The authors have no financial conflicts of interest.All animal procedures were approved by the Animal Care and Use Committee of Chung-Ang University (IACUC no. 2015-00016) in accordance with the Guide for the Care and Use of Agricultural Animals in Agricultural Research and the Guide for Care and Use of Laboratory Animals.

Background: Maternal exposure to the endocrine disruptor bisphenol A (BPA) has been linked to offspring reproductive abnormalities. However, exactly how BPA affects offspring fertility remains poorly understood., Objectives: The aim of the present study was to evaluate the effects of gestational BPA exposure on sperm function, fertility, and proteome profile of F1 spermatozoa in adult mice., Methods: Pregnant CD-1 mice (F0) were gavaged with BPA at three different doses (50 μg/kg bw/day, 5 mg/kg bw/day, and 50 mg/kg bw/day) on embryonic days 7 to 14. We investigated the function, fertility, and related processes of F1 spermatozoa at postnatal day 120. We also evaluated protein profiles of F1 spermatozoa to monitor their functional affiliation to disease., Results: BPA inhibited sperm count, motility parameters, and intracellular ATP levels in a dose-dependent manner. These effects appeared to be caused by reduced numbers of stage VIII seminiferous epithelial cells in testis and decreased protein kinase A (PKA) activity and tyrosine phosphorylation in spermatozoa. We also found that BPA compromised average litter size. Proteins differentially expressed in spermatozoa from BPA treatment groups are known to play a critical role in ATP generation, oxidative stress response, fertility, and in the pathogenesis of several diseases., Conclusions: Our study provides mechanistic support for the hypothesis that gestational exposure to BPA alters sperm function and fertility via down-regulation of tyrosine phosphorylation through a PKA-dependent mechanism. In addition, we anticipate that the BPA-induced changes in the sperm proteome might be partly responsible for the observed effects in spermatozoa. Citation: Rahman MS, Kwon WS, Karmakar PC, Yoon SJ, Ryu BY, Pang MG. 2017. Gestational exposure to bisphenol-A affects the function and proteome profile of F1 spermatozoa in adult mice. Environ Health Perspect 125:238-245; http://dx.doi.org/10.1289/EHP378., Competing Interests: The authors declare they have no actual or potential competing financial interests.

Mortality in ducks and geese caused by highly pathogenic avian influenza A(H5N1) infection had not been previously identified in Bangladesh. In June-July 2011, we investigated mortality in ducks, geese and chickens with suspected H5N1 infection in a north-eastern district of the country to identify the aetiologic agent and extent of the outbreak and identify possible associated human infections. We surveyed households and farms with affected poultry flocks in six villages in Netrokona district and collected cloacal and oropharyngeal swabs from sick birds and tissue samples from dead poultry. We conducted a survey in three of these villages to identify suspected human influenza-like illness cases and collected nasopharyngeal and throat swabs. We tested all swabs by real-time RT-PCR, sequenced cultured viruses, and examined tissue samples by histopathology and immunohistochemistry to detect and characterize influenza virus infection. In the six villages, among the 240 surveyed households and 11 small-scale farms, 61% (1789/2930) of chickens, 47% (4816/10 184) of ducks and 73% (358/493) of geese died within 14 days preceding the investigation. Of 70 sick poultry swabbed, 80% (56/70) had detectable RNA for influenza A/H5, including 89% (49/55) of ducks, 40% (2/5) of geese and 50% (5/10) of chickens. We isolated virus from six of 25 samples; sequence analysis of the hemagglutinin and neuraminidase gene of these six isolates indicated clade 2.3.2.1a of H5N1 virus. Histopathological changes and immunohistochemistry staining of avian influenza viral antigens were recognized in the brain, pancreas and intestines of ducks and chickens. We identified ten human cases showing signs compatible with influenza-like illness; four were positive for influenza A/H3; however, none were positive for influenza A/H5. The recently introduced H5N1 clade 2.3.2.1a virus caused unusually high mortality in ducks and geese. Heightened surveillance in poultry is warranted to guide appropriate diagnostic testing and detect novel influenza strains., (© 2015 Blackwell Verlag GmbH.)

Background: Globally, human astroviruses (HAstVs) have emerged as another common cause of non-bacterial acute gastroenteritis. Limited data exist on the epidemiology and genetic diversity of HAstVs in Bangladesh., Objective: We describe the epidemiology of HAstV-associated diarrhea among hospitalized patients, including HAstV genotypes, clinical symptoms and co-infecting pathogens., Study Design: Stool samples were collected from an ongoing diarrhea etiology surveillance during 2010-2012. HAstV was detected using RT-PCR and positive samples were subsequently tested for other common viral and bacterial pathogens. Phylogenetic analysis was performed and genotyped HAstV sequences were compared with previously reported Bangladeshi HAstV strains., Results: Of 826 fecal specimens, HAstV was detected in 26 cases (3.1%) and the majority of these cases (92%) was observed in children under 3 years of age. For 6 out of the 26 cases (23%) no other co-infecting pathogens were observed, whereas for the 20 remaining cases (77%) a variety of other known enteric viral and bacterial pathogens were observed. Based on the overlap region between ORF1b (RdRp) and ORF2 (capsid), five different genotypes (HAstV-1, -2, -3, -5 and -6) were identified circulating during the study period, with HAstV-1 being the predominant type. Genetic analysis revealed that HAstV-1 strains detected in this study were distantly related (<90% similarity of the capsid protein on the nt level) with HAstV-1 strains previously reported from Bangladesh., Conclusion: Our study provides an epidemiological overview and genetic diversity of HAstVs associated with acute diarrhea in Bangladesh., (Copyright © 2013 Elsevier B.V. All rights reserved.)

To explore Bangladesh's ability to detect novel influenza, we examined a series of laboratory-confirmed pandemic (H1N1) 2009 cases. During June-July 2009, event-based surveillance identified 30 case-patients (57% travelers); starting July 29, sentinel sites identified 252 case-patients (1% travelers). Surveillance facilitated response weeks before the spread of pandemic (H1N1) 2009 infection to the general population.