Liver and pancreatic-targeted interleukin-22 as a therapeutic for metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is the most prevalent cause of liver disease worldwide, with a single approved therapeutic. Previous research has shown that interleukin-22 (IL-22) can suppress ß-cell stress, reduce local islet inflammation, restore appropriate insulin production, reverse hyperglycemia, and ameliorate insulin resistance in preclinical models of diabetes. In clinical trials long-acting forms of IL-22 have led to increased proliferation in the skin and intestine, where the IL-22RA1 receptor is highly expressed. To maximise beneficial effects whilst reducing the risk of epithelial proliferation and cancer, we designed short-acting IL-22-bispecific biologic drugs that successfully targeted the liver and pancreas. Here we show 10-fold lower doses of these bispecific biologics exceed the beneficial effects of native IL-22 in multiple preclinical models of MASH, without off-target effects. Treatment restores glycemic control, markedly reduces hepatic steatosis, inflammation, and fibrogenesis. These short-acting IL-22-bispecific targeted biologics are a promising new therapeutic approach for MASH.

Evaluating arsenic contamination in northwestern Bangladesh: A GIS-Based assessment of groundwater vulnerability and human health impacts.

One of the biggest environmental worries in the world today is the risk of arsenic (As) contamination in groundwater. The Atomic Absorption Spectrometer (AAS) was used in this work to assess the As content in groundwater samples from 38 shallow (27 m) tubewells in northwest Bangladesh to determine the existing situation, potential source(s), and likely health risk of As and other important water quality parameters. The range of arsenic concentrations (µgL-1) was troublesome and greater than the WHO recommended level for drinking water, ranging from 0.50 to 164 (mean ± SD: 20.22 ± 36.46). In groundwater, the concentrations of Fe, and Mn vary from 0.04 to 52.75 mgL-1 (mean ± SD: 4.23 ± 9.68), and 0.23 to 3.27 mgL-1 (mean ± SD: 1.10 ± 0.67). The obtained groundwater samples have pH values ranging from 5.9 to 7.1, which indicates a somewhat acidic to neutral character. Major cations have an average abundance that is as follows: Ca2+ > Mg2+ > Na+ > K+, while major anions have an average abundance that is as follows: HCO3- > Cl- > SO42- > NO3-; Ca2+ and HCO3- are the main cation and anion, respectively. The groundwater in the Rajarampur village was deemed unfit for drinking or irrigation based on analyses of water quality performed using the entropy water quality index. The Ca-HCO3 type of water, in which Ca2+ and HCO3- are the main positive ions and negative ions, is suggested by the Piper tri-linear diagram. It was discovered that silicate weathering regulates the hydro-geochemical activities in groundwater using a bi-variate examination of several hydro-chemical variables. Four major clusters were observed for the water sample. According to reductive dissolution processes and principal component analysis, the arsenic in groundwater is geogenic in origin. Arsenic is discharged from sediment to groundwater by reductive dissolution of FeOOH and MnOOH, as shown by the modest connection between As, Fe, and Mn. The United Nations Environmental Protection Agency's (USEPA) suggested value for probable cancer risk assessment was 10-6, however the probable cancer risk assessment found a higher value, indicating that the population in the study region was at high risk for cancer. Remedial measures for arsenic mitigation include removing arsenic from groundwater after it is extracted, searching for alternative aquifers, and implementing various water-supply technologies such as dugwells, deep tubewells, pond-sand filters, and rainwater harvesting systems.

Assessment of human health risk from potentially toxic elements and predicting groundwater contamination using machine learning approaches.

The Rooppur Nuclear Power Plant (RNPP) at Ishwardi, Bangladesh is planning to go into operation within 2024 and therefore, adjacent areas of RNPP is gaining adequate attention from the scientific community for environmental monitoring purposes especially for water resources management. However, there is a substantial lack of literature as well as environmental datasets for earlier years since very little was done at the beginning of the RNPP's construction phase. Therefore, this study was conducted to assess the potential toxic elements (PTEs) contamination in the groundwater and its associated health risk for residents at the adjacent part of the RNPP during the year of 2014-2015. For the purposes of achieving the aim of the study, groundwater samples were collected seasonally (dry and wet season) from nine sampling sites and afterwards analyzed for water quality indicators such as temperature (Temp.), pH, electrical conductivity (EC), total dissolved solid (TDS), total hardness (TH) and for PTEs including Iron (Fe), Manganese (Mn), Copper (Cu), Lead (Pb), Chromium (Cr), Cadmium (Cd) and Arsenic (As). This study adopted the newly developed Root Mean Square water quality index (RMS-WQI) model to assess the scenario of contamination from PTEs in groundwater whereas the human health risk assessment model was utilized to quantify the risk of toxicity from PTEs. In most of the sampling sites, PTEs concentration was found higher during the wet season than the dry season and Fe, Mn, Cd and As exceeded the guideline limit for drinking water. The RMS score mostly classified the groundwater in terms of PTEs contamination into "Fair" condition. The non-carcinogenic risks (expressed as Hazard Index-HI) revealed that around 44% and 89% of samples for adults and 67% and 100% of samples for children exceeded the threshold limit set by USEPA (HI > 1) and possessed risks through the oral pathway during dry and wet season, respectively. Furthermore, the calculated cumulative HI score was found higher for children than the adults throughout the study period. In terms of carcinogenic risk (CR) from PTEs, the magnitude of risk decreased following the pattern of Cr > As > Cd. Although the current study is based on old dataset, the findings might serve as a baseline for monitoring purposes to reduce future hazardous impact from the power plant.

Cannabidiol - Help and hype in targeting mucosal diseases.

Cannabidiol (CBD) is one of the most commonly utilised phytocannabinoids due to its non-psychoactive and multiple potential therapeutic properties and its non-selective pharmacology. Recent studies have demonstrated efficacy of CBD in some types of drug resistant epilepsies in combination with other therapies; comparative efficacy to other agents or placebo has been hoped for anxiety, chronic pain, and inflammatory disorders based on animal data. Although CBD products are generally treated as a restricted substance, these are being eased, partially in response to significant growth in CBD product usage and increased production but more due to emerging evidence about its safety and pharmacological properties. Currently, only one CBD product (Epidiolex®) has been approved by the Australian Therapeutic Goods Administration and US Food and Drug Administration. CBD has demonstrated promise in alleviating gut and lung diseases in vitro; however, its physicochemical properties pose a significant barrier to achieving pharmacological effects in in vivo and clinical trials. Improving CBD formulations and delivery methods using technologies including self-emulsifying emulsion, nano and micro particles could overcome these shortfalls and improve its efficacy. This review focuses on the therapeutic potential of CBD in gastrointestinal and lung diseases from the available in vitro, in vivo, and clinical research. We report on identified research gaps and obstacles in the development of CBD-based therapeutics, including novel delivery methods.

Investigation of pathogenic germline variants in gastric cancer and development of "GasCanBase" database.

BACKGROUND: Gastric cancer, which is also known as stomach cancer, can be influenced by both germline and somatic mutations. Non-synonymous Single Nucleotide Polymorphisms (nsSNPs) in germline have long been reported to play a pivotal role in cancer progression. AIM: The aim of this study is to examine the nsSNP in GC-associated genes. The study also aims to develop a database with extensive information regarding the nsSNPs in the GC-associated genes and their impacts. METHODS AND RESULTS: A total of 34,588 nsSNPs from 1,493,460 SNPs of the 40 genes were extracted from the available SNP database. Drug binding and energy minimization were examined by molecular docking and YASARA. To validate the existence of the germline CDH1 gene mutation (rs34466743) in the isolated blood DNA of gastric cancer (GC) patients, polymerase chain reaction (PCR) and DNA sequencing were performed. According to the results of the gene network analysis, 17 genes may interact with other types of cancer. A total of 11,363 nsSNPs were detected within the 40 GC genes. Among these, 474 nsSNPs were predicted to be damaging and 40 to be the most damaging. The SNPs in domain regions were thought to be strong candidates that alter protein functions. Our findings proposed that most of the selected nsSNPs were within the domains or motif regions. Free Energy Deviation calculation of protein structure pointed toward noteworthy changes in the structure of each protein that can demolish its natural function. Subsequently, drug binding confirmed the structural variation and the ineffectiveness of the drug against the mutant model in individuals with these germline variants. Furthermore, in vitro analysis of the rs34466743 germline variant from the CDH1 gene confirmed the strength and robustness of the pipeline that could expand the somatic alteration for causing cancer. In addition, a comprehensive gastric cancer polymorphism database named "GasCanBase" was developed to make data available to researchers. CONCLUSION: The findings of this study and the "GasCanBase" database may greatly contribute to our understanding of molecular epidemiology and the development of precise therapeutics for gastric cancer. GasCanBase is available at: https://www.gascanbase.com/.

Polyphenolic Carbon Quantum Dots with Intrinsic Reactive Oxygen Species Amplification for Two-Photon Bioimaging and In Vivo Tumor Therapy.

Recent studies indicate that mitochondrial dysfunctions and DNA damage have a critical influence on cell survival, which is considered one of the therapeutic targets for cancer therapy. In this study, we demonstrated a comparative study of the effect of polyphenolic carbon quantum dots (CQDs) on in vitro and in vivo antitumor efficacy. Dual emissive (green and yellow) shape specific polyphenolic CQDs (G-CQDs and Y-CQDs) were synthesized from easily available nontoxic precursors (phloroglucinol), and the antitumor property of the as-synthesized probe was investigated as compared to round-shaped blue emissive CQDs (B-CQDs) derived from well-reported precursor citric acid and urea. The B-CQDs had a nuclei-targeting property, and G-CQDs and Y-CQDs had mitochondria-targeting properties. We have found that the polyphenol containing CQDs (at a dose of 100 µg mL-1) specifically attack mitochondria by excess accumulation, altering the metabolism, inhibiting branching pattern, imbalanced Bax/Bcl-2 homeostasis, and ultimately generating oxidative stress levels, leading to oxidative stress-induced cell death in cancer cells in vitro. We show that G-CQDs are the main cause of oxidative stress in cancer cells because of their ability to produce sufficient •OH- and 1O2 radicals, evidenced by electron paramagnetic resonance spectroscopy and a terephthalic acid test. Moreover, the near-infrared absorption properties of the CQDs were exhibited in two-photon (TP) emission, which was utilized for TP cellular imaging of cancer cells without photobleaching. The in vivo antitumor test further discloses that intratumoral injection of G-CQDs can significantly augment the treatment efficacy of subcutaneous tumors without any adverse effects on BalB/c nude mice. We believe that shape-specific polyphenolic CQD-based nanotheranostic agents have a potential role in tumor therapy, thus proving an insight on treatment of malignant cancers.

Exploring potential anti-inflammatory effects of medicinal cannabis.

PURPOSE: Inflammation is thought to play a key role in malignant disease and may play a significant part in the expression of cancer-related symptoms. Cannabidiol (CBD) is a bioactive compound in cannabis and is reported to have significant anti-inflammatory properties. METHOD: Serial C-reactive protein (CRP) levels were measured in all participants recruited to a randomised controlled trial of CBD versus placebo in patients with symptoms related to advanced cancer. A panel of inflammatory cytokines was measured over time in a subset of these patients. RESULTS: There was no difference between the two arms in the trajectory of CRP or cytokine levels from baseline to day 28. CONCLUSION: We were unable to demonstrate an anti-inflammatory effect of CBD in cancer patients. TRIAL REGISTRATION: ANZCTR 26180001220257, registered 20/07/2018.

MUC13 Cell Surface Mucin Limits Salmonella Typhimurium Infection by Protecting the Mucosal Epithelial Barrier.

BACKGROUND & AIMS: MUC13 cell surface mucin is highly expressed on the mucosal surface throughout the intestine, yet its role against bacterial infection is unknown. We investigated how MUC13 impacts Salmonella typhimurium (S Tm) infection and elucidated its mechanisms of action. METHODS: Muc13-/- and wild-type littermate mice were gavaged with 2 isogenic strains of S Tm after pre-conditioning with streptomycin. We assessed clinical parameters, cecal histology, local and systemic bacterial load, and proinflammatory cytokines after infection. Cecal enteroids and epithelial cell lines were used to evaluate the mechanism of MUC13 activity after infection. The interaction between bacterial SiiE and MUC13 was assessed by using siiE-deficient Salmonella. RESULTS: S Tm-infected Muc13-/- mice had increased disease activity, histologic damage, and higher local and systemic bacterial loads. Mechanistically, we found that S Tm binds to MUC13 through its giant SiiE adhesin and that MUC13 acts as a pathogen-binding decoy shed from the epithelial cell surface after pathogen engagement, limiting bacterial invasion. In addition, MUC13 reduces epithelial cell death and intestinal barrier breakdown by enhancing nuclear factor kappa B signaling during infection, independent of its decoy function. CONCLUSIONS: We show for the first time that MUC13 plays a critical role in antimicrobial defense against pathogenic S Tm at the intestinal mucosal surface by both acting as a releasable decoy limiting bacterial invasion and reducing pathogen-induced cell death. This further implicates the cell surface mucin family in mucosal defense from bacterial infection.

Effects of membrane potentials on the electroporation of giant unilamellar vesicles.

Living organisms maintain a resting membrane potential, which plays an important role in various biophysical and biological processes. In the context of medical applications, irreversible electroporation (IRE) is a non-thermal and minimally invasive technique that utilizes precisely controlled electric field pulses of micro- to millisecond durations to effectively ablate cancer and tumor cells. Previous studies on IRE-induced rupture of cell-mimetic giant unilamellar vesicles (GUVs) have primarily been conducted in the absence of membrane potentials. In this study, we investigated the electroporation of GUVs, including parameters such as the rate constant of rupture and the probability of rupture, in the presence of various negative membrane potentials. The membranes of GUVs were prepared using lipids and channel forming proteins. As the membrane potential increased from 0 to -90 mV, the rate constant of rupture showed a significant increase from (7.5 ± 1.6)×10-3 to (35.6 ± 5.5)×10-3 s-1. The corresponding probability of rupture also exhibited a notable increase from 0.40 ± 0.05 to 0.68 ± 0.05. To estimate the pore edge tension, the electric tension-dependent logarithm of the rate constant was fitted with the Arrhenius equation for different membrane potentials. The presence of membrane potential did not lead to any significant changes in the pore edge tension. The increase in electroporation is reasonably explained by the decrease in the prepore free energy barrier. The choice of buffer used in GUVs can significantly influence the kinetics of electroporation. This study provides valuable insights that can contribute to the application of electroporation techniques in the biomedical field.

Interleukin-22 suppresses major histocompatibility complex II in mucosal epithelial cells.

Major histocompatibility complex (MHC) II is dynamically expressed on mucosal epithelial cells and is induced in response to inflammation and parasitic infections, upon exposure to microbiota, and is increased in chronic inflammatory diseases. However, the regulation of epithelial cell-specific MHC II during homeostasis is yet to be explored. We discovered a novel role for IL-22 in suppressing epithelial cell MHC II partially via the regulation of endoplasmic reticulum (ER) stress, using animals lacking the interleukin-22-receptor (IL-22RA1), primary human and murine intestinal and respiratory organoids, and murine models of respiratory virus infection or with intestinal epithelial cell defects. IL-22 directly downregulated interferon-γ-induced MHC II on primary epithelial cells by modulating the expression of MHC II antigen A α (H2-Aα) and Class II transactivator (Ciita), a master regulator of MHC II gene expression. IL-22RA1-knockouts have significantly higher MHC II expression on mucosal epithelial cells. Thus, while IL-22-based therapeutics improve pathology in chronic disease, their use may increase susceptibility to viral infections.

Impacts of seasonal variations and wastewater discharge on river quality and associated human health risks: A case of northwest Dhaka, Bangladesh.

Surface water pollution caused by the discharge of effluents from industrial estates has become a major concern for Dhaka (Bangladesh). This study aims to have a concise look at the severe river water pollution, mainly from effluents discharged from the tannery village. Effluent samples were collected from five ejected points, including the central effluent treatment plant (CETP), twenty adjacent river water, and two pond water nearby Hemayetpur, Savar. Thirty-one parameters have been observed at these sampling points for three seasons, from April 2021 to January 2022. The results obtained from water quality indices, i.e., water quality index (WQI), entropy water quality index (EWQI), and irrigation water quality index (IWQI), show that most studied surface water samples ranked "unsuitable" for consumption, irrigation, and anthropogenic purposes. The highest health risk was observed downstream of Hemayetpur city at the Savar CETP discharge site, indicating higher levels of heavy metal in the river water following the tannery village. Carcinogenic and non-carcinogenic human health risks could be triggered mainly by water consumption as concentrations of arsenic (As), chromium (Cr), nickel (Ni), and lead (Pb) exceeded the upper benchmark of 1 × 10-4 for adults and children. The results of the carcinogenic risk assessment revealed that children were more vulnerable to health hazards, and quick corrective action is required to control the increased levels of heavy metals at all sample locations. Therefore, through bioaccumulation, human health and the environment are affected in these areas. Using river water for consumption, household work, or even irrigation purposes is not advisable. This study's result highlighted that properly implementing compatible policies and programs is required to improve effluent treatment methods and provide biodegradability to the Dhaleshwari River.

Virus-like silica nanoparticles enhance macromolecule permeation in vivo.

Nanoparticle based permeation enhancers have the potential to improve the oral delivery of biologics. Recently, solid silica nanoparticles were discovered to improve the intestinal permeability of peptides and proteins via transient opening of the gut epithelium. In this study, we have developed small-sized (∼60 nm) virus-like silica nanoparticles (VSNP) as a reversible and next generation non-toxic permeation enhancer for oral delivery of biologics. Our results show that the anionic VSNP showed a better permeation-enhancing effect than the same sized spherical Stöber silica nanoparticles (∼60 nm) by enhancing the apparent insulin permeability by 1.3-fold in the Caco-2 monolayer model and by 1.2-fold in the Caco-2/MTX-HT-29 co-culture model. In vivo experiments in healthy mice demonstrated that anionic VSNP significantly enhanced the permeation of fluorescently labelled 4 kDa dextran after oral administration compared to Stöber nanoparticles and positively charged VSNP. The results indicated that the nanoscale surface roughness is an important consideration when designing nanoparticle-based permeation enhancers. Overall, our study shows for the first time that small-sized (∼60 nm) VSNP with nanoscale surface roughness can be used as a non-toxic permeation enhancer for oral delivery of therapeutic peptides and proteins.

Hydrogeochemical evaluation, groundwater contamination and associated health risk in southern Tangail, Bangladesh.

Water pollution is a worldwide concern that has growing severe in developed and developing nations. Increasing groundwater pollution threatening both the physical and environmental health of billions of people as well as economic progress. Consequently, hydrogeochemistry, water quality and potential health risk assessment is crucial for water resource management. The study area comprises Jamuna Floodplain (Holocene deposit) area in the west and the Madhupur tract (Pleistocene deposit) area in the eastern part. Total 39 groundwater samples were collected from the study area and were analyzed for physicochemical parameters, hydrogeochemical, trace metals, and isotopic composition. The water types are mainly Ca-HCO3- to Na-HCO3- types. The isotopic compositions (δ18O‰ and δ2H‰) analysis traces the recent recharge in Floodplain area from rainwater and no recent recharge in Madhupur tract. The concentration of NO3-, As, Cr, Ni, Pb, Fe, and Mn in shallow and intermediate aquifer at the Floodplain area exceed the WHO-2011 permissible limit and is lower at deep Holocene and Madhupur tract aquifer. The integrated weighted water quality index (IWQI) exposed groundwater from shallow and intermediate aquifer are unsuitable for drinking and deep Holocene aquifer and Madhupur tract are suitable for drinking purposes. PCA analysis confirmed that anthropogenic activity is dominant in shallow and intermediate aquifers. The non-carcinogenic and carcinogenic risk for adults and children is due to oral and dermal exposure. The non-carcinogenic risk evaluation revealed that the mean hazard index (HI) values range from 0.009742 to 16.37 for adults and 0.0124-20.83 for children, respectively, and most groundwater samples from shallow and intermediate aquifers exceed the permissible limit (HI>1). The carcinogenic risk ranges from 2.71 × 10-6-0.014 for adults and 3.44 × 10-6-0.017 for children via oral consumption and 7.09 × 10-11-1.18 × 10-6 for adults and 1.25 × 10-10-2.09 × 10-6 for children via dermal exposure. Spatial distribution shows the presence of trace metal and associated health risk is high in shallow and intermediate aquifer (Holocene) than in the deep (Holocene) Madhupur tract (Pleistocene). The study implies that effective water management will ensure safe drinking water for the future generation of people.

A 3D Bioprinted Nanoengineered Hydrogel with Photoactivated Drug Delivery for Tumor Apoptosis and Simultaneous Bone Regeneration via Macrophage Immunomodulation.

One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects owing to the recruitment of local infection and delayed angiogenesis. Herein, a 3D printable multi-functional hydrogel composing polyphenolic carbon quantum dots (CQDs, 100 µg mL-1 ) and gelatin methacryloyl (GelMA, 12 wt%) is reported for robust angiogenesis, bone regeneration and anti-tumor therapy. The CQDs are synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene. The 3D printed GelMA-CQDs hydrogels display typical shear-thinning behavior with excellent printability. The fabricated hydrogel displayed M2 polarization of macrophage (Raw 264.7) cells via enhancing anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs are able to produce vessel-like structures after 14 d of incubation. Furthermore, the 3D printed hydrogel scaffolds also show remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm-2 ) irradiation with controlled release of antitumor drugs (≈49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, it is anticipated that the tissue regeneration and healing ability with therapeutic potential of the GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation.

Bacterial and viral etiology of acute respiratory infection among the Forcibly Displaced Myanmar Nationals (FDMNs) in fragile settings in Cox's Bazar- a prospective case-control study.

The leading infectious cause of death in children worldwide is lower acute respiratory infection (LARI), particularly pneumonia. We enrolled a total of 538 acute respiratory infection (ARI) cases according to WHO criteria and age-sex matched 514 controls in the Forcibly Displaced Myanmar National (FDMN) refugee camps in Cox's Bazar, Bangladesh, between June 2018 and March 2020 to investigate the role of bacteria, viruses, and their co-infection patterns and observe Streptococcus pneumoniae (S. pneumoniae) serotype distribution. According to the etiological findings, children ≤5 years of age have a higher bacterial positivity (90%) and viral positivity (34%) in nasopharyngeal samples (NPS) compared to those >5 years of age, in both ARI cases as well as for the control group. Among the bacteria, S. pneumoniae was predominant in both cases and controls (85% and 88%). Adenovirus (ADV)(34), influenza virus A and B (IFV-A, B)(32,23), and respiratory syncytial virus (RSV)(26) were detected as the highest number among the viruses tested for the ARI cases. The total number of viruses was also found higher in ≤5 years of age group. Within this group, positive correlation was observed between bacteria and viruses but negative correlation was observed between bacteria. Both single and co-infection for viruses were found higher in the case group than the control group. However, co-infection was significantly high for Streptococcus aureus (S. aureus) and Haemophilus influenzae b (H. influenza b) (p<0.05). Additionally, semi-quantitative bacterial and viral load was found higher for the ARI cases over control considering Cycle threshold (Ct)≤30. Pathogen identification from blood specimens was higher by qRT-PCR than blood culture (16% vs 5%, p<0.05). In the S. pneumoniae serotype distribution, the predominant serotypes in ARI cases were 23F, 19A, 16F, 35B, 15A, 20 and 10F, while 11A, 10A, 34, 35A and 13 serotypes were predominant in the control group. Pathogen correlation analysis showed RSV positively correlated with human metapneumovirus (HMPV), S. aureus and H. influenza b while S. pneumoniae was negatively correlated with other pathogens in ≤5 years age group of ARI cases. However, in >5 years age group, S. aureus and H. influenza b were positively correlated with IFVs, and S. pneumoniae was positively correlated with HMPV and ADV. Logistic regression data for viruses suggested among the respondents in cases were about 4 times more likely to be RSV positive than the control. Serotype distribution showed 30% for PCV10 serotypes, 41% for PCV13 and 59% for other serotypes. Also, among the 40 serotypes of S. pneumoniae tested, the serotypes 22F, Sg24, 9V, 38, 8, and 1 showed strong positive correlation with viruses in the case group whereas in the control group, it was predominant for serotypes 14, 38, 17F and 39 ARI cases were prevalent mostly in monsoon, post-monsoon, and winter periods, and peaked in September and October. Overall these region-specific etiological data and findings, particularly for crisis settings representing the FDMNs in Cox's Bazar, Bangladesh, is crucial for disease management and disease prevention control as well as immunization strategies more generally in humanitarian crisis settings.

Clinicopathological Patterns of Malignant Solid Tumors in Adult Patients: A Hospital-Based Study From Bangladesh.

BACKGROUND: Solid malignant tumors are abnormal masses of tissue that usually do not contain any cysts or liquid areas. The causation of these tumors is multifactorial, and the disease process differs at different sites. AIM: This study aims to determine the clinicopathological patterns of malignant solid tumors in adult patients admitted into the department of internal medicine of a tertiary care hospital in Bangladesh. METHOD: This cross-sectional study was conducted between January 2018 and June 2018 at the Department of Medicine, Dhaka Medical College Hospital, Bangladesh. We recorded the complete socio-demographic characteristics, clinical patterns, and pathological characteristics of malignant solid tumors in adult patients. RESULTS: A total of 100 patients with confirmed malignant solid tumors were included in our study. The mean age of the patients was 47.5 years (SD: ±4.20); most of them (27%) were between 58 and 67 years of age. Male patients constitute 59% of the total study sample. Most of the patients were of the middle socio-economic class (59%) and most of them (61%) were nonsmokers. Among the patient diagnoses, 19% had lung cancer, 29.27% had breast cancer, and in 14%, lymphoma (tumor arising from the lymphatic system) was the common solid tumor. Lung cancer was found to be the most common form of cancer in males. Additionally, the majority of those diagnosed with lung cancer smoked. Breast cancer was found to be the most common type of cancer in females. CONCLUSION: This study reflects that solid malignant tumors can affect any socio-economic class of people. Based on findings in our study as well as others, prevention efforts should focus on the reduction in tobacco use and the incorporation of other lifestyle changes, such as diet modification and exercise. Additionally, the incorporation of economic factors and how they affect cancer presentation in different contexts is crucial.

Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma.

The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy.

Integrating Metabolomics and Gene Expression Underlying Potential Biomarkers Compounds Associated with Antioxidant Activity in Southern Grape Seeds.

Different southern grape (Muscadine) genotypes (Muscadinia rotundifolia Michx.) were evaluated for their contents of metabolites in ripe berries. The metabolome study identified 331 metabolites in ripening skin and seed tissues. The major chemical groups were organic acids, fatty acyls, polyketides, and organic heterocycle compounds. The metabolic pathways of the identified metabolite were mainly arginine biosynthesis, D-glutamine, D-glutamate metabolism, alanine, aspartate metabolism, aminoacyl-tRNA biosynthesis, and citrate cycle. Principal component analysis indicated that catechin, gallic acid, and epicatechin-3-gallate were the main metabolites existing in muscadine seed extracts. However, citramalic and malic acids were the main metabolites contributing to muscadine skin extracts. Partial least-squares discriminant analysis (VIP > 1) described 25 key compounds indicating the metabolome in muscadine tissues (skin and seed). Correlation analysis among the 25 compounds and oxidation inhibition activities identified five biomarker compounds that were associated with antioxidant activity. Catechin, gallic acid, epicatechin-3-gallate, fertaric acid, and procyanidin B1 were highly associated with DPPH, FRAP, CUPRAC, and ABTS. The five biomarker compounds were significantly accumulated in the seed relative to the skin tissues. An evaluation of 15 antioxidant-related genes represented by the 3-dehydroquinate dehydratase (DHD), shikimate kinase (SK), chalcone synthase (CHS), anthocyanidin reductase (ANR), laccase (LAC), phenylalanine ammonia-lyase (PAL), dihydroflavonol 4-reductase (DFR), 3-dehydroquinate synthase (DHQS), chorismate mutase (CM), flavanone-3-hydroxylase (F3H), cinnamoyl-CoA reductase (CCR), cinnamyl alcohol dehydrogenase (CAD), leucoanthocyanidin reductase (LAR), gallate 1-ß-glucosyltransferase (UGT), and anthocyanidin 3-O-glucosyltransferase (UFGT) encode critical enzymes related to polyphenolics pathway throughout four developmental stages (fruit-set FS, véraison V, ripe-skin R, and ripe-seed; S) in the C5 genotype demonstrated the dramatic accumulation of all transcripts in seed tissue or a developmental stage-dependent manner. Our findings suggested that muscadine grape seeds contain essential metabolites that could attract the attention of those interested in the pharmaceutical sector and the plant breeders to develop new varieties with high nutraceutical value.

Spatial distribution, water quality, human health risk assessment, and origin of heavy metals in groundwater and seawater around the ship-breaking area of Bangladesh.

The concentrations of eleven heavy metals (Pb, Cd, Cr, Fe, Mn, Zn, Cu, Ni, Co, As, and Ag) were assessed in both groundwater and seawater collected from the ship-breaking industrial area of Bangladesh using an atomic absorption spectrometer. The investigation aimed to estimate the water quality and pollution level employing several indices, and its associated health risks for the first time in that area. This study found that Cd, Cr, Fe, Pb, Mn, and Ni were higher in both groundwater and seawater compared with WHO standards. Based on the WQI (water quality index) and EWQI (entropy water quality index) classifications, the quality of most of the groundwater is extremely poor or unsuitable for drinking purposes. Furthermore, the HPI (heavy metal pollution index), HEI (heavy metal evaluation index), and CD (degree of contamination) values of most groundwater and all seawater samples exhibit a higher degree of pollution. In addition, the results of NI (Nemerow pollution index) come to an end that both groundwater and seawater in the study area are mostly polluted by Fe, Mn, Pb, Cr, and Cd. Although the HI (hazard quotient index) values of almost all studied heavy metals in both cases of adults and children are within the safe limit, the HI value of Cr for an adult is near the threshold limit and the maximum HI value of Cr for children exceeds this limit. The carcinogenic risk reveals that Cr, Pb, As, and Cd produce detrimental effects on local people through the direct ingestion of groundwater. The pollution source is identified using principal component analysis and a Pearson correlation matrix as being primarily anthropogenic and attributed to intensive ship-breaking activities or other industries in the area.

Understanding Cancer Caregiving and Predicting Burden: An Analytics and Machine Learning Approach.

Cancer caregivers are often informal family members who may not be prepared to adequately meet the needs of patients and often experience high stress along with significant physical, emotional, and financial burdens. Accurate prediction of caregiver's burden level is highly valuable for early intervention and support. In this study, we used several machine learning approaches to build prediction models from the National Alliance for Caregiving/AARP dataset. We performed data cleansing and imputation on the raw data to give us a working dataset of cancer caregivers. Then a series of feature selection methods were used to identify predictive risk factors for burden level. Using supervised machine learning classifiers, we achieved reasonably good prediction performance (Accuracy ∼ 0.94; AUC ∼ 0.97; F1∼ 0.93). We identify a small set of 15 features that are strong predictors of burden and can be used to build Clinical Decision Support Systems.