Antioxidants activities of phytochemicals perspective modulation of autophagy and apoptosis to treating cancer.

The study of chemicals extracted from natural sources should be encouraged due to the significant number of cancer deaths each year and the financial burden imposed by this disease on society. The causes of almost all cancers involve a combination of lifestyle, environmental factors, and genetic and inherited factors. Modern medicine researchers are increasingly interested in traditional phytochemicals as they hold potential for new bioactive compounds with medical applications. Recent publications have provided evidence of the antitumor properties of phytochemicals, a key component of traditional Chinese medicine, thereby opening new avenues for their use in modern medicine. Various studies have demonstrated a strong correlation between apoptosis and autophagy, two critical mechanisms involved in cancer formation and regulation, indicating diverse forms of crosstalk between them. Phytochemicals have the ability to activate both pro-apoptotic and pro-autophagic pathways. Therefore, understanding how phytochemicals influence the relationship between apoptosis and autophagy is crucial for developing a new cancer treatment strategy that targets these molecular mechanisms. This review aims to explore natural phytochemicals that have demonstrated anticancer effects, focusing on their role in regulating the crosstalk between apoptosis and autophagy, which contributes to uncontrolled tumor cell growth. Additionally, the review highlights the limitations and challenges of current research methodologies while suggesting potential avenues for future research in this field.

Effect of low oxygen stress on the metabolic responses of tomato fruit cells.

Postharvest losses of fruits and vegetables can occur due to cell breakdown and browning during controlled atmosphere storage as a result of low oxygen (O2) stress. Therefore, the study was designed to better understand the underlying mechanisms of the response of isolated tomato fruit cells incubated at low O2 (hypoxic and anoxic) conditions as a model system. The O2 stress conditions used for the experiment were based on the results of the Michaelis-Menten constant (Km) of respiration. A total of 56 polar metabolites belonging mainly to different functional groups, including amino acids, organic acids, sugars and sugar alcohols, were identified using GC-MS. O2 stress stimulated the biosynthesis of most of the free amino acids while decreasing the synthesis of most of the organic acids (especially those linked to the tricarboxylic acid cycle), sugars (except for ribose) and other nitrogen-containing compounds. The down-regulation of these TCA cycle metabolites served to provide energy to ensure the survival of the cell. Increases in the sugar alcohol levels and induction of fermentative metabolism were observed under low O2 stress. By employing multivariate statistics, metabolites were identified that were essential to the oxygen stress response and establishing the correlation between metabolite abundance, oxygen levels, and incubation period were achievable. A higher correlation was observed between the O2 levels and most of the metabolites.

Knowledge, attitudes, and practices regarding antibiotic use in Bangladesh: Findings from a cross-sectional study.

BACKGROUND: Escalating antibiotic resistance presents a notable worldwide dilemma, pointing a large involvement of general population. The objective of this study was to assess knowledge, attitudes, and practices regarding the utilization of antibiotics among Bangladeshi residents. METHODS: A cross-sectional study, conducted from January 01 to April 25, 2022, included 1,947 Bangladeshi adults with a history of antibiotic use, via online surveys and face-to-face interviews using a pretested semi-structured questionnaire. Descriptive statistics, Chi-square tests, and multivariate linear regression models were employed. RESULTS: Mean scores for knowledge, attitudes, and practices were 6.59±1.20, 8.34±1.19, and 12.74±2.59, with correct rates of 73.22%, 92.67%, and 57.91%. Positive predictors for knowledge included being unmarried (ß = 0.10, p = 0.001), higher education (College: ß = 0.09, p = 0.025; Bachelor: ß = 0.22, p<0.001; Master or above: ß = 0.14, p<0.001), various professions (student: ß = 0.57, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.53, p<0.001; businessman: ß = 0.31, p<0.001; unemployed: ß = 0.15, p<0.001), and residing in semi-urban (ß = 0.32, p<0.001) or urban areas (ß = 0.15, p<0.001). Positive predictors for attitudes included being married (ß = 0.18, p<0.001), specific professions (student: ß = 1.06, p<0.001; housewife: ß = 0.33, p<0.001; employee: ß = 0.86, p<0.001; businessman: ß = 0.37, p<0.001; unemployed: ß = 0.47, p<0.001), higher SES (Lower-middle: ß = 0.22, p<0.001; Middle: ß = 0.26, p<0.001), and residing in semi-urban areas (ß = 0.18, p<0.001); negative predictors included higher education (College: ß = -0.12, p = 0.001; Master or above: ß = -0.09, p = 0.008) and being rich (ß = -0.13, p<0.001). Positive predictors for practices included being married (ß = 0.18, p<0.001), specific professions (student: ß = 0.32, p<0.001; employee: ß = 0.43, p<0.001; businessman: ß = 10, p = 0.034; unemployed: ß = 0.11, p = 0.009), and higher SES (Lower-middle: ß = 0.14, p = 0.009; Middle: ß = 0.38, p<0.001; Higher-middle: ß = 0.15, p = 0.008); negative predictors included higher education (College: ß = -0.21, p<0.001), being rich (ß = -0.12, p<0.001), residing in semi-urban (ß = -0.14, p<0.001) or urban areas (ß = -0.16, p<0.001). CONCLUSIONS: Participants exhibited adequate knowledge and positive attitudes but lagged behind in proper practice of antibiotic use. Proper initiatives should be tailored to enhance prudent antibiotic use and mitigate the risk of antimicrobial resistance.

Maintaining glucose integrity ex-vivo: Impact of preanalytical specimen handling.

BACKGROUND: Adopting the WHO protocol for glucose analysis is arguably impractical in the routine clinical setting. Deviations may develop due to a lack of understanding regarding the impact of glycolysis on the accuracy of results. AIM: We sought to assess the stability of glucose in two different blood collection tubes (BCT), BD Vacutainer® FX 'Fl-Ox' and Greiner Vacuette® FC-Mix 'FC-Mix' stored at room temperature (RT:18-22°C) and 4°C over 8.5 days. METHOD: Each participant provided venous whole blood collected into 51 BCTs; 'Fl-Ox' (n = 26) and 'FC-Mix' (n = 25). One Fl-Ox sample from each participant was handled according to the WHO recommended method. The remaining BCTs were stored at 4°C/RT prior to analyses at designated study timepoints. Glucose was measured using the hexokinase assay on the Cobas® 8000 platform. RESULTS: Participants (n = 8, Male = 2) were aged 24-56 years. Plasma glucose measured in FI-Ox BCTs according to the WHO sample-handling method had a median concentration of 5.73 mmol/L (Range: 5.39-10.37 mmol/L). Glucose decreased by greater than minimal difference (>0.26 mmol/L) in blood collected into Fl-Ox and stored @4°C/RT within 24 h of phlebotomy. FC-Mix BCT maintained glucose <0.26 mmol/L @4°C over a period of 8.5 days and up to 4 days @RT when compared to the WHO recommended method. CONCLUSION: Glucose in FC-Mix BCT stored @4°C demonstrated the best agreement with results determined using the WHO specifications. When FC-Mix tubes were stored @RT, glucose was stable for 4 days. These findings suggest that the FC-Mix BCT effectively inhibits glycolysis and should be introduced into routine clinical practice.

Physicochemical cues are not potent regulators of human dermal fibroblast trans-differentiation.

Due to their inherent plasticity, dermal fibroblasts hold great promise in regenerative medicine. Although biological signals have been well-established as potent regulators of dermal fibroblast function, it is still unclear whether physiochemical cues can induce dermal fibroblast trans-differentiation. Herein, we evaluated the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human dermal fibroblast cultures. Our data indicate that tissue culture plastic and collagen type I coating increased cell proliferation and metabolic activity. None of the assessed in vitro microenvironment modulators affected cell viability. Anisotropic surface topography induced bidirectional cell morphology, especially on more rigid (1,000 kPa and 130 kPa) substrates. Macromolecular crowding increased various collagen types, but not fibronectin, deposition. Macromolecular crowding induced globular extracellular matrix deposition, independently of the properties of the substrate. At day 14 (longest time point assessed), macromolecular crowding downregulated tenascin C (in 9 out of the 14 groups), aggrecan (in 13 out of the 14 groups), osteonectin (in 13 out of the 14 groups), and collagen type I (in all groups). Overall, our data suggest that physicochemical cues (such surface topography, substrate rigidity, collagen coating and macromolecular crowding) are not as potent as biological signals in inducing dermal fibroblast trans-differentiation.

Antiviral foods in the battle against viral infections: Understanding the molecular mechanism.

Viruses produce a variety of illnesses, which may also cause acute respiratory syndrome. All viral infections, including COVID-19, are associated with the strength of the immune system. Till now, traditional medicine or vaccines for most viral diseases have not been effective. Antiviral and immune-boosting diets may provide defense against viral diseases by lowering the risk of infection and assisting rapid recovery. The purpose of this review was to gather, analyze, and present data based on scientific evidence in order to provide an overview of the mechanistic insights of antiviral bioactive metabolites. We have covered a wide range of food with antiviral properties in this review, along with their potential mechanism of action against viral infections. Additionally, the opportunities and challenges of using antiviral food have been critically reviewed. Bioactive plant compounds, not only help in maintaining the body's normal physiological mechanism and good health but are also essential for improving the body's immunity and therefore can be effective against viral diseases. These agents fight viral diseases either by incorporating the body's defense mechanism or by enhancing the cell's immune system. Regular intake of antiviral foods may prevent future pandemic and consumption of these antiviral agents with traditional medicine may reduce the severity of viral diseases. Therefore, the synergistic effect of antiviral foods and medication needs to be investigated.

Safety and Preliminary Efficacy of Mesenchymal Stromal Cell (ORBCEL-M) Therapy in Diabetic Kidney Disease: A Randomized Clinical Trial (NEPHSTROM).

SIGNIFICANCE STATEMENT: Mesenchymal stromal cells (MSCs) may offer a novel therapy for diabetic kidney disease (DKD), although clinical translation of this approach has been limited. The authors present findings from the first, lowest dose cohort of 16 adults with type 2 diabetes and progressive DKD participating in a randomized, placebo-controlled, dose-escalation phase 1b/2a trial of next-generation bone marrow-derived, anti-CD362 antibody-selected allogeneic MSCs (ORBCEL-M). A single intravenous (iv) infusion of 80×10 6 cells was safe and well-tolerated, with one quickly resolved infusion reaction in the placebo group and no subsequent treatment-related serious adverse events (SAEs). Compared with placebo, the median annual rate of decline in eGFR was significantly lower with ORBCEL-M, although mGFR did not differ. The results support further investigation of ORBCEL-M in this patient population in an appropriately sized phase 2b study. BACKGROUND: Systemic therapy with mesenchymal stromal cells may target maladaptive processes involved in diabetic kidney disease progression. However, clinical translation of this approach has been limited. METHODS: The Novel Stromal Cell Therapy for Diabetic Kidney Disease (NEPHSTROM) study, a randomized, placebo-controlled phase 1b/2a trial, assesses safety, tolerability, and preliminary efficacy of next-generation bone marrow-derived, anti-CD362-selected, allogeneic mesenchymal stromal cells (ORBCEL-M) in adults with type 2 diabetes and progressive diabetic kidney disease. This first, lowest dose cohort of 16 participants at three European sites was randomized (3:1) to receive intravenous infusion of ORBCEL-M (80×10 6 cells, n =12) or placebo ( n =4) and was followed for 18 months. RESULTS: At baseline, all participants were negative for anti-HLA antibodies and the measured GFR (mGFR) and estimated GFR were comparable between groups. The intervention was safe and well-tolerated. One placebo-treated participant had a quickly resolved infusion reaction (bronchospasm), with no subsequent treatment-related serious adverse events. Two ORBCEL-M recipients died during follow-up of causes deemed unrelated to the trial intervention; one recipient developed low-level anti-HLA antibodies. The median annual rate of kidney function decline after ORBCEL-M therapy compared with placebo did not differ by mGFR, but was significantly lower by eGFR estimated by the Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease equations. Immunologic profiling provided evidence of preservation of circulating regulatory T cells, lower natural killer T cells, and stabilization of inflammatory monocyte subsets in those receiving the cell therapy compared with placebo. CONCLUSIONS: Findings indicate safety and tolerability of intravenous ORBCEL-M cell therapy in the trial's lowest dose cohort. The rate of decline in eGFR (but not mGFR) over 18 months was significantly lower among those receiving cell therapy compared with placebo. Further studies will be needed to determine the therapy's effect on CKD progression. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrial.gov NCT02585622 .

Effects of barley seedling powder on rheological properties of dough and quality of steamed bread.

In order to find the optimal share of barley seedling powder (BSP) to improve the rheological properties of wheat dough and physico-chemical properties of steamed bread (SB), BSP was added with wheat flour at various proportions (2-10%). Results showed that with the increasing amount of BSP additive, the farinograph index (86.33-123), dough stability (9.37-12.63 min), and dough development time (6.23-7.63 min) in blend flour increased. Similarly, with the increasing BSP, SB became darker and more greenish, and the total flavonoid content increased. The content of chlorophyll-b, and total chlorophyll demonstrated a faster increase than that of chlorophyll-a. The hardness and chewability of SB improved as well whereas the springiness increased first and then decreased. The best springiness and gumminess of SB were found with 2% and 8% BSP additives respectively. 2%, 4%, and 6% addition of BSP resulted in a slight fluctuation in the bound water quantity than 8% and 10% BSP additive. No new compound formation was confirmed by Infrared analysis and there was only a heat and mass transfer process. Results from this study indicated that SB with improved quality attributes can be prepared from wheat flour fortified with BSP at 2-4%.

Heavy metals contamination in shrimp and crab from southwest regions in Bangladesh: Possible health risk assessment.

Shrimp and Crab, important sources of protein, are currently being adversely affected by the rising industrialization, which has led to higher levels of heavy metals. The goal of this study was to evaluate the health risks of contamination associated with nine heavy metals (Cd, Pb, Cu, Cr, Zn, Ni, As, Al, and Fe) in two species of shrimp (Macrobrachium rosenbergii and Metapenaeus monoceros) and one species of crab (Scylla serrata) that were collected from the Khulna, Satkhira, and Bagerhat areas of Bangladesh. Inductively coupled plasma-optical emission spectrometry (ICP-OES) was used for the study. The results showed that all metal concentrations in shrimp and crab samples were below the recommended level, indicating that ingestion of these foods would not pose any substantial health risks to individuals. To evaluate the non-carcinogenic health risks, the target hazard quotient (THQ) and hazard index (HI) were determined, and the target cancer risk (TR) was utilized to evaluate the carcinogenic health risks. From the health point of view, this study showed that crustaceans obtained from the study sites were non - toxic (THQ and HI < 1), and long-term, continuous intake is unlikely to pose any significant health hazards (TR = 10-7-10-5) from either carcinogenic or non-carcinogenic effects.

RRM2 and CDC6 are novel effectors of XBP1-mediated endocrine resistance and predictive markers of tamoxifen sensitivity.

BACKGROUND: Endocrine-resistant breast cancers have elevated expression of XBP1, where it drives endocrine resistance by controlling the expression of its target genes. Despite the in-depth understanding of the biological functions of XBP1 in ER-positive breast cancer, effectors of endocrine resistance downstream of XBP1 are poorly understood. The aim of this study was to identify the XBP1-regulated genes contributing to endocrine resistance in breast cancer. METHODS: XBP1 deficient sub-clones in MCF7 cells were generated using the CRISPR-Cas9 gene knockout strategy and were validated using western blot and RT-PCR. Cell viability and cell proliferation were evaluated using the MTS assay and colony formation assay, respectively. Cell death and cell cycle analysis were determined using flow cytometry. Transcriptomic data was analysed to identify XBP1-regulated targets and differential expression of target genes was evaluated using western blot and qRT-PCR. Lentivirus and retrovirus transfection were used to generate RRM2 and CDC6 overexpressing clones, respectively. The prognostic value of the XBP1-gene signature was analysed using Kaplan-Meier survival analysis. RESULTS: Deletion of XBP1 compromised the upregulation of UPR-target genes during conditions of endoplasmic reticulum (EnR) stress and sensitized cells to EnR stress-induced cell death. Loss of XBP1 in MCF7 cells decreased cell growth, attenuated the induction of estrogen-responsive genes and sensitized them to anti-estrogen agents. The expression of cell cycle associated genes RRM2, CDC6, and TOP2A was significantly reduced upon XBP1 deletion/inhibition in several ER-positive breast cancer cells. Expression of RRM2, CDC6, and TOP2A was increased upon estrogen stimulation and in cells harbouring point-mutants (Y537S, D538G) of ESR1 in steroid free conditions. Ectopic expression of RRM2 and CDC6 increased cell growth and reversed the hypersensitivity of XBP1 KO cells towards tamoxifen conferring endocrine resistance. Importantly, increased expression of XBP1-gene signature was associated with poor outcome and reduced efficacy of tamoxifen treatment in ER-positive breast cancer. CONCLUSIONS: Our results suggest that RRM2 and CDC6 downstream of XBP1 contribute to endocrine resistance in ER-positive breast cancer. XBP1-gene signature is associated with poor outcome and response to tamoxifen in ER-positive breast cancer.

Chronic Kidney Disease Is Characterized by Expansion of a Distinct Proinflammatory Intermediate Monocyte Subtype and by Increased Monocyte Adhesion to Endothelial Cells.

SIGNIFICANCE STATEMENT: CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function. It also demonstrates that human monocyte adhesion to endothelial layers and responses to specific inflammatory migration signals are enhanced in CKD. These findings offer insights into the mechanisms of CKD-associated intravascular and localized inflammation and may suggest potential targets for therapeutic interventions. BACKGROUND: Cardiovascular disease (CVD) in patients with CKD is associated with increased circulating intermediate monocytes (IMs). Dysregulation of monocyte maturation and function is associated with CKD and its complications, but it is incompletely characterized. METHODS: To explore monocyte repertoire abnormalities in CKD, we studied properties of monocyte subpopulations, including IM subpopulations distinguished by HLA-DR expression level, in individuals with or without CKD. Using flow cytometry, we profiled monocyte populations in blood samples from adults with CKD, healthy volunteers (HVs), and patient controls (PCs) with high CVD risk. Monocyte subpopulations were also derived from single-cell RNA-sequencing profiles of paired blood and biopsy samples from kidney transplant recipients. We quantified intracellular cytokine production, migration, and endothelial adhesion in ex vivo assays of PBMCs. RESULTS: Of four predefined blood monocyte subpopulations, only HLA-DR hi IMs were increased in individuals with CKD compared with HVs and PCs. In HVs and patients with CKD, LPS-stimulated HLA-DR hi IMs isolated from blood produced higher amounts of TNF and IL-1 ß than other monocyte populations. Single-cell analysis revealed four monocyte clusters common to blood and kidneys, including an HLA-DR hi IM-like cluster that was enriched in kidneys versus blood. Migration toward CCL5 and CX3CL1 and adhesion to primary endothelial cell layers were increased in monocyte subpopulations in individuals with CKD compared with HVs. Monocyte adhesion to endothelial cells was partly dependent on CX3CR1/CX3CL1 interaction. CONCLUSIONS: CKD is associated with an increased number of a distinctive proinflammatory IM subpopulation and abnormalities of monocyte migration and endothelial adhesion. Dysregulated monocyte maturation and function may represent targetable factors contributing to accelerated CVD in CKD.

The synergistic effect of physicochemical in vitro microenvironment modulators in human bone marrow stem cell cultures.

Modern bioengineering utilises biomimetic cell culture approaches to control cell fate during in vitro expansion. In this spirit, herein we assessed the influence of bidirectional surface topography, substrate rigidity, collagen type I coating and macromolecular crowding (MMC) in human bone marrow stem cell cultures. In the absence of MMC, surface topography was a strong modulator of cell morphology. MMC significantly increased extracellular matrix deposition, albeit in a globular manner, independently of the surface topography, substrate rigidity and collagen type I coating. Collagen type I coating significantly increased cell metabolic activity and none of the assessed parameters affected cell viability. At day 14, in the absence of MMC, none of the assessed genes was affected by surface topography, substrate rigidity and collagen type I coating, whilst in the presence of MMC, in general, collagen type I α1 chain, tenascin C, osteonectin, bone sialoprotein, aggrecan, cartilage oligomeric protein and runt-related transcription factor were downregulated. Interestingly, in the presence of the MMC, the 1000 kPa grooved substrate without collagen type I coating upregulated aggrecan, cartilage oligomeric protein, scleraxis homolog A, tenomodulin and thrombospondin 4, indicative of tenogenic differentiation. This study further supports the notion for multifactorial bioengineering to control cell fate in culture.

Effects of superheated steam processing on the physicochemical properties of sea rice bran.

Sea rice bran powder is a new type of instant food additive. Currently, its solubility is low, and its flavor is not pleasant. Superheated steam cooking is a promising treatment in cellulose-rich substances, which essentially improves quality. To gain better sea rice bran powder, physicochemical properties of sea rice bran were investigated using 100 °C, 110 °C, 120 °C, and 130 °C superheated steam treatments for 10, 20, 30, and 40 min. After the treatment, these samples were cooled down, dried, and milled to assess sea rice bran powder's product qualities. Profiles of odor, taste, aroma, and aliphatic acids were determined using e-nose, e-tongue, and gas chromatography-mass spectroscopy. Results revealed that superheated steam brought new profiles of odors and tastes for consumers. Superheated steam treatment was found to decrease swelling capacity. Methane (2,2,4,6,6-pentamethyl, heptane) was seen as a significant odor component, whereas umami and bitterness were considered considerable taste components. Superheated steam treatment retained higher content of aliphatic acids: saturated fatty acids 218-204 mg/100 g and unsaturated fatty acids 830-781 mg/100 g. This study discovered that superheated steam is suitable for processing rice bran as food ingredients; 100 °C-120 °C and 10-30 min could be suggested for suitable cooking sea rice bran.

Effect of Multi-Mode Thermosonication on the Microbial Inhibition and Quality Retention of Strawberry Clear Juice during Storage at Varied Temperatures.

Strawberry juice, which is rich in nutrients and charming flavor, is favored by consumers. To explore whether multi-mode thermosonication (MTS) can ensure the quality stability of strawberry clear juice (SCJ) during storage, the effects of microbial inhibition, enzyme activity, and physicochemical properties of SCJ pretreated by MTS were evaluated during storage at 4, 25, and 37 °C in comparison with thermal pretreatment (TP) at 90 °C for 1 min. The MTS, including dual-frequency energy-gathered ultrasound pretreatment (DEUP) and flat sweep-frequency dispersive ultrasound pretreatment (FSDUP), were conducted at 60 °C for 5 and 15 min, respectively. Results showed that the total phenols, flavonoids, anthocyanins, ascorbic acid, and DPPH free radical scavenging ability of SCJ decreased during the storage period. The control sample of SCJ was able to sage for only 7 days at 4 °C based on the microbiological quality, while the FSDUP and DEUP group extended the storage period up to 21 and 14 days, respectively. The polyphenol oxidase in SCJ pretreated by MTS did not reactivate during the storage period. The MTS remarkably (p < 0.05) reduced the color deterioration, browning degree, and nutrient degradation during the storage period. Moreover, the FSDUP group exhibited the maximum shelf life with a minimum loss of quality, demonstrating that it was the most suitable processing method for obtaining high-quality SCJ. It can be concluded that the MTS has the potential to inhibit enzymatic browning, inactivating microorganisms, preserve original quality attributes, and prolong the shelf life of SCJ.

Reference intervals for clinical biochemistry and haematology tests during normal pregnancy.

BACKGROUND: Pregnancy induces physiological changes which affect biochemical and haematological parameters. As the significance of laboratory test results change throughout pregnancy, the reference interval (RI) or key result interpretive guide should be specific to pregnancy. This study sought to establish trimester-specific-RIs for routine biochemical and haematological tests in healthy white European women with singleton pregnancies with comparison to RIs for non-pregnant European adults. METHODS: A retrospective analysis of a prospective longitudinal single-centre study of healthy pregnant women conducted between November 2018 and December 2020 in a tertiary academic hospital with approximately 3000 births annually. Inclusion criteria: signed informed consent, age ≥18 years, white European, body mass index (BMI) <25 kg/m2, blood pressure <140/90mmHg, non-smoker, no previous pathology or gestational diabetes. Trimester defined as T1: up to 13 weeks + 6 days, T2: 14-27 weeks + 6 days and T3: ≥28-41 weeks + 6 days. Baseline demographics, anthropometric and laboratory measurements were recorded. In total, 31 biochemical and 10 haematological ISO15189:2012 accredited tests were measured using Roche Cobas® and Sysmex XN-9100™ analysers, respectively. RIs were established according to the International Federation of Clinical Chemistry (IFCC) recommended method. RESULTS: Apparently healthy pregnant women (n = 124) with bio-banked serum samples in each trimester were recruited. At the booking visit, 49.2% (n = 61) of participants were nulliparous, with median age of 34.4 (IQR: 31.3-37.3) years, gestational age of 89 (IQR: 84-93) days, BMI of 22.5 (IQR: 21.0-23.7) kg/m2 and systolic and diastolic blood pressure of 116 (110-125) mmHg and 67 (61-75) mmHg, respectively. CONCLUSIONS: Normative trimester-specific biological intervals for routinely requested biochemical and haematological medical laboratory tests were established. These RIs will be invaluable to result interpretation and the management of pregnant women.

Multimodal Hybrid Deep Learning Approach to Detect Tomato Leaf Disease Using Attention Based Dilated Convolution Feature Extractor with Logistic Regression Classification.

Automatic leaf disease detection techniques are effective for reducing the time-consuming effort of monitoring large crop farms and early identification of disease symptoms of plant leaves. Although crop tomatoes are seen to be susceptible to a variety of diseases that can reduce the production of the crop. In recent years, advanced deep learning methods show successful applications for plant disease detection based on observed symptoms on leaves. However, these methods have some limitations. This study proposed a high-performance tomato leaf disease detection approach, namely attention-based dilated CNN logistic regression (ADCLR). Firstly, we develop a new feature extraction method using attention-based dilated CNN to extract most relevant features in a faster time. In our preprocessing, we use Bilateral filtering to handle larger features to make the image smoother and the Ostu image segmentation process to remove noise in a fast and simple way. In this proposed method, we preprocess the image with bilateral filtering and Otsu segmentation. Then, we use the Conditional Generative Adversarial Network (CGAN) model to generate a synthetic image from the image which is preprocessed in the previous stage. The synthetic image is generated to handle imbalance and noisy or wrongly labeled data to obtain good prediction results. Then, the extracted features are normalized to lower the dimensionality. Finally, extracted features from preprocessed data are combined and then classified using fast and simple logistic regression (LR) classifier. The experimental outcomes show the state-of-the-art performance on the Plant Village database of tomato leaf disease by achieving 100%, 100%, 96.6% training, testing, and validation accuracy, respectively, for multiclass. From the experimental analysis, it is clearly demonstrated that the proposed multimodal approach can be utilized to detect tomato leaf disease precisely, simply and quickly. We have a potential plan to improve the model to make it cloud-based automated leaf disease classification for different plants.

Inhibition of Insulin Degrading Enzyme to Control Diabetes Mellitus and its Applications on some Other Chronic Disease: a Critical Review.

PURPOSE: This review aims to provide a precise perceptive of the insulin-degrading enzyme (IDE) and its relationship to type 2 diabetes (T2D), Alzheimer's disease (AD), obesity, and cardiovascular diseases. The purpose of the current study was to provide clear idea of treating prevalent diseases such as T2D, and AD by molecular pharmacological therapeutics rather than conventional medicinal therapy. METHODS: To achieve the aims, molecular docking was performed using several softwares such as LIGPLOT+, Python, and Protein-Ligand Interaction Profiler with corresponding tools. RESULTS: The IDE is a large zinc-metalloprotease that breakdown numerous pathophysiologically important extracellular substrates, comprising amyloid ß-protein (Aß) and insulin. Recent studies demonstrated that dysregulation of IDE leads to develop AD and T2D. Specifically, IDE regulates circulating insulin in a variety of organs via a degradation-dependent clearance mechanism. IDE is unique because it was subjected to allosteric activation and mediated via an oligomer structure. CONCLUSION: In this review, we summarised the factors that modulate insulin reformation by IDE and interaction of IDE and some recent reports on IDE inhibitors against AD and T2D. We also highlighted the latest signs of progress of the function of IDE and challenges in advancing IDE- targetted therapies against T2D and AD.

Reference intervals for commonly requested biochemical and haematological parameters in a healthy Irish adult Caucasian population.

INTRODUCTION: In laboratory medicine, reference intervals (RIs) are key decision support tools used to guide the clinical interpretation of numerical test results. Best practice suggests each laboratory establishes RIs in the local population prior to introducing an assay into routine clinical practice. AIM: The aim of this study was to define RIs for frequently requested biochemical/haematological parameters in a healthy adult Irish Caucasian population. METHODS: A cross-sectional study of non-pregnant apparently healthy volunteers was conducted. Baseline demographics, anthropometric and laboratory measurements were recorded. In total, 37 commonly requested biochemical (serum, n = 26) and haematological (venous blood, n = 11) ISO15189:2012 accredited tests were analysed, using the Roche Cobas® Sebia Capillarys 3 Tera and Siemens Advia® 2120i platforms following standard operating procedures. RIs were defined according to the International Federation of Clinical Chemistry (IFCC) recommended method. RESULTS: Of 208 apparently healthy volunteers, 76 failed to meet the study inclusion criteria. The reference population comprised of 132 participants (males: n = 65, 49.2%) with a median age of 29.7 (18.1-62.2) years. RIs for the majority of biochemical/haematological parameters were broadly in accord with those provided by Pathology Harmony (UK)/Irish RI Harmonisation Project and the manufacturer Roche Diagnostics. However, the established RI defined for HbA1c: 27-37 mmol/mol was markedly different from that quoted nationally, HbA1c: 20-42 mmol/mol. CONCLUSION: Normative biological intervals established in a healthy adult Irish population for 37 commonly requested biochemical/haematological parameters will be a valuable aid to result interpretation in clinical laboratories after appropriate verification in accordance with ISO 15189: 2012.

Multiplex Serum Biomarker Assays Improve Prediction of Renal and Mortality Outcomes in Chronic Kidney Disease.

BACKGROUND: We investigated the predictive value of 11 serum biomarkers for renal and mortality end points in people with CKD. METHODS: Adults with CKD (n=139) were enrolled from outpatient clinics between February 2014 and November 2016. Biomarker quantification was performed using two multiplex arrays on a clinical-grade analyzer. Relationships between biomarkers and renal and mortality end points were investigated by random forests and Cox proportional hazards regression. RESULTS: The cohort was 56% male. The mean age was 63 years and median (IQR) CKD-EPI eGFR was 33 (24-51) ml/min per BSA. A total of 56 (40%) people developed a composite end point defined as ≥40% decline in eGFR, doubling of serum creatinine, RRT, or death over median (IQR) follow-up of 5.4 (4.7-5.7) years. Prediction of the composite end point was better with random forests trained on serum biomarkers compared with clinical variables (area under the curve of 0.81 versus 0.78). The predictive performance of biomarkers was further enhanced when considered alongside clinical variables (area under the curve of 0.83 versus 0.81 for biomarkers alone). Patients (n=27, 19%) with high soluble TNF receptor-1 (≥3 ng/ml) and neutrophil gelatinase-associated lipocalin (≥156 ng/ml), coupled with low complement 3a des-arginine (<2368 ng/ml), almost universally (96%) developed the composite renal and mortality end point. C-reactive protein (adjusted hazard ratio, 1.4; 95% CI, 1.1 to 1.8), neutrophil gelatinase-associated lipocalin (adjusted hazard ratio, 2.8; 95% CI, 1.3 to 6.1) and complement 3a desarginine (adjusted hazard ratio, 0.6; 95% CI, 0.4 to 0.96) independently predicted time to the composite end point. CONCLUSIONS: Outpatients with the triad of high soluble TNF receptor-1 and neutrophil gelatinase-associated lipocalin coupled with low complement 3a des-arginine had high adverse event rates over 5-year follow-up. Incorporation of serum biomarkers alongside clinical variables improved prediction of CKD progression and mortality. Our findings require confirmation in larger, more diverse patient cohorts.