👤 Ghazi Mohammad Sayedur Rahman

Therapeutic peptides are emerging as promising adjuncts in the management of orthopaedic injuries, grounded in their ability to modulate molecular signaling networks central to cellular medicine. By acting on key pathways such as PI3K/Akt, mTOR, MAPK, TGF-β, and AMPK, peptides exert influence over tissue regeneration, inflammation resolution, and neuromuscular recovery. Wound-healing peptides such as BPC-157, TB-500, and GHK-Cu promote angiogenesis, integrin-mediated extracellular matrix remodeling, and fibroblast activation, whereas growth hormone secretagogues like ipamorelin, CJC-1295, tesamorelin, sermorelin, and AOD-9604 activate IGF-1 signaling and satellite cell repair. Recovery-enhancing agents such as epithalon, delta sleep-inducing peptide, and pinealon target circadian and mitochondrial regulators, and neuroactive peptides like selank, semax, and dihexa enhance brain-derived neurotrophic factor and HGF/c-Met pathways critical to neuroplasticity. Although preclinical studies are promising, there is a current lack of clinical trials. This review integrates current mechanistic insights with orthopaedic relevance, emphasizing safety, efficacy, and future directions for responsible integration into musculoskeletal care. Show less

Atherosclerosis, affecting the aorta, cervical, or intracranial arteries, is a common cause of stroke. Previous studies have shown a strong link between high Lp(a) levels and atherosclerotic stroke due to intracranial atherosclerotic disease, implicating Lp(a) in disease development and progression. The precise role of Lp(a) in stroke subtypes remains unclear, although smaller isoform sizes and oxidized phospholipids on Lp(a) are associated with the disease presence. To clarify Lp(a)'s connection with ischemic stroke subtypes, we evaluated various plasma biomarkers previously linked to Lp(a) and disease. We used stored plasma samples and data from 244 participants enrolled in an acute ischemic stroke registry at Columbia University Medical Center in New York. Plasma Lp(a) concentrations, apolipoprotein B100 (APOB), and oxidized phospholipids were measured via enzyme-linked immunosorbent assay. APO(a) isoform size was measured via gel electrophoresis. Stroke subtypes were classified based on etiologies using clinical and imaging data. Adjusted multivariate logistic regression models were built to assess associations between Lp(a)-related biomarkers and stroke subtype. In participants with acute ischemic stroke, high Lp(a) concentrations, percentage of APOB in Lp(a), and OxPL-APO(a) concentrations were significantly associated with the presence of atherosclerotic stroke compared to those with non-atherosclerotic strokes [OR = 1.30 ( In addition to Lp(a) concentrations, the percentage of APOB in Lp(a), and OxPL-APO(a) concentrations are positively associated with acute atherosclerotic ischemic stroke, specifically ECAD. Show less

The repeated failure of amyloid therapies highlights a core misunderstanding of Alzheimer's disease (AD) origins. A new metabolic paradigm now positions impaired brain metabolism-not protein accumulation-as the central, early driver. Key evidence shows cerebral glucose hypometabolism emerges decades before symptoms, linked to brain insulin resistance ("type 3 diabetes") and mitochondrial dysfunction. The APOE ε4 allele worsens lipid defects thereby, accelerating the progression of AD pathology. These disruptions-alongside gut-brain axis issues-create a self-reinforcing cycle that fuels amyloid β (Aβ), tau, neuroinflammation, and synaptic loss. This framework integrates with the neuron-centric model, explaining disease heterogeneity and the inadequacy of single-target drugs. This review particularly highlights the metabolic perspective in AD, underscoring the need for a radical therapeutic shift: from late stage protein clearance strategies to early, multimodal interventions that restore metabolic homeostasis and disrupt the entire pathogenic continuum. Show less

Alzheimer's disease (AD) is characterized by the gradual deterioration of cognitive functions, speech impairment, and memory loss. It can potentially be treated by targeting the beta-site amyloid precursor protein cleavage enzyme 1 (BACE1), which plays a key role in amyloid plaque formation, neurofibrillary tangles, and hyperphosphorylated tau protein. Current drugs have limitations in terms of safety, efficacy, and blood-brain barrier permeability. In view of this, this study was designed to determine the potential inhibitors of the BACE1 enzyme by virtual screening using a curated library of 415 natural products including terpenoids, phenolic compounds, and alkaloids from different medicinal plants. Based on the docking score and interaction analysis, 50 compounds were selected for the downstream analysis, such as ligand binding interactions, pharmacokinetics, druglikness and physicochemical parameters. Among the lead compounds, Palmatine (compound 45) and Berberine (compound 49), demonstrated optimal drug-likeness and blood-brain barrier permeability among the top compounds. 2-[(9Z,12Z)-heptadeca-9,12-dienyl]-6-hydroxybenzoic acid (compound 4) was inactive in most toxicity parameters. Pharmacophore analysis revealed that Palmatine and Berberine share similar features with the standard, highlighting their potential as effective compounds. Furthermore, structural chemistry analysis provided insights on their shared isoquinoline alkaloid framework, illustrating their structural similarities. Molecular dynamics simulations confirmed the stability of the Palmatine-BACE1 and Berberine-BACE1 complexes during a 50 ns production run. Overall, these findings highlighted the potential of Palmatine and Berberine as promising candidates for the experimental validation and the development of the drugs for the treatment of AD. Show less

Acute myeloid leukemia (AML) is a complex hematologic malignancy with multiple disease subgroups defined by somatic mutations and heterogeneous outcomes. Although genome-wide association studies (GWAS) have identified a small number of common genetic variants influencing AML risk, the heritable component of this disease outside of familial susceptibility remains largely undefined. Here, we perform a meta-analysis of 4 published GWAS plus 2 new GWAS, totaling 4710 AML cases and 12 938 controls. We identify a new genome-wide significant risk locus for pan-AML at 2p23.3 (rs4665765; P = 1.35 × 10-8; EFR3B, POMC, DNMT3A, and DNAJC27), which also significantly associates with patient survival (P = 6.09 × 10-3). Our analysis also identifies 3 new genome-wide significant risk loci for disease subgroups, including AML with deletions of chromosome 5 and/or 7 at 1q23.3 (rs12078864; P = 7.0 × 10-10; DUSP23) and cytogenetically complex AML at 2q33.3 (rs12988876; P = 3.28 × 10-8; PARD3B) and 2p21 (rs79918355; P = 1.60 × 10-9; EPCAM). We also investigated loci previously associated with the risk of clonal hematopoiesis (CH) or CH of indeterminate potential and identified several variants associated with the risk of AML. Our results further inform on AML etiology and demonstrate the existence of disease subgroup specific risk loci. Show less

Increased lipoprotein(a) (Lp[a]) is a genetically determined causal risk factor for atherosclerotic cardiovascular disease (ASCVD). Historically, Lp(a) testing has been uncommon in Australia. This study aims to assess the prevalence and trends in Lp(a) testing in Australia, and the associated patient characteristics. This retrospective cross-sectional study examined over 1.1 million de-identified electronic medical records from patients seen in the Advara HeartCare network from 2011 to 2022. Adult patients from 2011 to 2021 comprised the historical group, while those from 2022 formed the baseline group. A natural language processing algorithm identified patients with ASCVD and Lp(a) testing, and extracted demographics, characteristics, and cardiovascular comorbidities from clinical letters. Patients with ASCVD in the baseline group were followed up for 18 months to assess trends in Lp(a) testing. Testing Lp(a) was infrequent among patients with ASCVD but increased gradually over time. In the historical cohort, of 164,121 patients identified with ASCVD, 1,501 (0.9%) underwent Lp(a) testing. Of these, 44.8% had Lp(a) levels <30 mg/dL, and 25.0% >90 mg/dL. In the baseline cohort, 1,460 (2.6%) of 55,427 patients with ASCVD underwent Lp(a) testing. Of 730 with recorded Lp(a) values, 30.2% had Lp(a) levels ≥70 mg/dL, and 86.8% were on lipid-lowering therapy. Dyslipidaemia was the most common comorbidity (72.8%), followed by Stage 1 or 2 chronic kidney disease (40.1%). During 18-month follow-up from the baseline period, 329 additional patients underwent Lp(a) testing in 2023. The study revealed that Lp(a) testing is underutilised among patients with ASCVD in Australia despite recent guidelines recommending it. This emphasises the need to expand Lp(a) testing to improve health outcomes for high-risk patients. Show less

Eichhornia crassipes (Mart.) Solms, also known as Pontederia crassipes Mart, has traditionally been used for its sedative, antipsychotic, and memory-enhancing properties. However, its effects against Alzheimer's disease (AD) remain unexplored. Therefore, this study aimed to investigate the in vitro anti-AD properties of methanol (MEECF), ethanol (EEECF), and ethyl acetate (EAEECF) extracts of E. crassipes flowers and to identify potential multi-modal anti-AD phytocompounds using computational drug discovery targeting acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Initially, 204 phytocompounds were metabolically annotated through GC-MS analysis of the extracts, and their functional groups and chemical nature were identified using PPS and FT-IR analysis, respectively. Molecular docking identified two hit phytocompounds (CID 4970, fumarine, and CID 106962, cyclopentanemethanamine, 5-amino-2,2,4-trimethyl-) in MEECF and EEECF, which exhibited higher binding affinities toward all targets compared to the control drug donepezil (-5.721 kcal/mol). Further molecular analysis revealed favorable pharmacokinetics, drug-likeness, and no toxicity for these two phytocompounds. Molecular dynamics simulation confirmed their binding stability to the active sites of AChE, BChE, and BACE-1, exhibiting multi-modal inhibitory activity. MEECF, EEECF, and EAEECF showed concentration-dependent antioxidant and AChE and BChE inhibition, supporting the in silico results regarding oxidative stress and cholinergic pathways. These findings suggest the anti-AD potential of E. crassipes flowers, with fumarine and cyclopentanemethanamine, 5-amino-2, 2, 4-trimethyl- identified as multi-modal inhibitors of AChE, BChE, and BACE-1. However, further in vivo research is required to comprehensively evaluate their efficacy in combating AD. Show less

Regulatory B cells (Bregs) contribute to immune homeostasis via IL-10-dependent and independent pathways. To dissect additional mediators, we investigated splenic derived GM-CSF/IL-15 fusokine (GIFT15)-induced Bregs in experimental autoimmune encephalomyelitis (EAE) using transcriptomics and functional validation. Bulk RNA-seq of splenic Bregs revealed upregulation of Ccl3, GzmB, and Il27 subunits compared to resting B cells. Functional studies showed that CCL3-deficient Bregs failed to suppress disease, whereas GzmB-deficient Bregs retained efficacy, and IL-27 receptor signaling in recipients was dispensable. Flow cytometry demonstrated that CCL3 expression correlated with FoxP3⁺ Treg and Tr1 expansion, along with CD206⁺ macrophage polarization. In the CNS, transient, tissue-dependent increases in oligodendroglial markers O4 and GalC were detected. Collectively, these findings identify CCL3 as a non-redundant effector of Breg-mediated protection, acting primarily through peripheral T-cell and myeloid remodeling, with secondary CNS impacts. These results highlight the translational potential of CCL3-competent, spleen-derived GIFT15 Bregs for therapeutic modulation of autoimmune demyelination. Show less

Despite advancements in treatment, coronary artery disease (CAD) remains a significant global health concern. Although lipoprotein(a) [Lp(a)] is recognized as a crucial cardiovascular risk factor associated with increased risk, the prognostic value of using Lp(a) levels in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) remains debatable. This review aimed to investigate the association between Lp(a) levels and recurrent ischemic events in patients with ACS undergoing PCI. This systematic review included studies with individuals aged ≥18 years diagnosed with ACS who underwent PCI and had Lp(a) measurements. The included studies were sourced from the PubMed database, with a focus on articles published between January 2020 and January 2025. Keywords related to Lp(a) and cardiovascular diseases were used in the search. Data extraction involved a review of titles and abstracts followed by quality assessment using the QUADAS-2 tool. The final analysis included 10 studies with a combined population of 20,896 patients from diverse regions, including Japan, India, Egypt, China, and South Korea. Key findings indicate that elevated Lp(a) levels are significantly associated with adverse cardiovascular outcomes, including myocardial infarction and mortality, both in hospital and during long-term follow-up. This review highlights Lp(a) as a critical biomarker for predicting recurrent cardiovascular events in ACS patients post-PCI. The consistent correlation between elevated Lp(a) levels and adverse outcomes underscores the necessity of routine monitoring and targeted management of Lp(a) to mitigate residual cardiovascular risk. Show less

Although low-density lipoprotein cholesterol (LDL-C) is established as the primary cardiovascular disease (CVD) risk factor, some individuals with LDL-C within desirable limits still develop coronary artery disease (CAD). Lipoprotein(a) (Lp(a)) has emerged as a genetically determined independent risk factor for CVD. This study aims to investigate Lp(a) by determining its association with coronary artery stenosis severity, identifying its ethnic-specific genetic determinants and assessing its relationship with an energy-dense dietary pattern. The PUTRA-CV study is a 3-year, multicentre, case-control observational study involving adult patients who have undergone coronary angiography. The primary outcome is the association between Lp(a) levels and the severity of angiographic CAD (assessed by Gensini or Syntax score). Secondary outcomes include the frequencies of Lp(a)-associated single nucleotide polymorphisms (SNPs) (rs10455872 and rs3798220) and the association between dietary patterns and Lp(a) levels. Lp(a) will be measured using a particle-enhanced immunoturbidimetric method, and SNPs will be genotyped using high-resolution melting. Dietary intake will be assessed using a validated semiquantitative food frequency questionnaire. Data will be analysed using SPSS. Descriptive statistics will be used to summarise population characteristics. Bivariate analyses will use chi-square (χ2), independent t-tests or Mann-Whitney U tests as appropriate. The independent association between Lp(a) and coronary artery stenosis severity will be determined using multivariable logistic regression, adjusting for confounders. Empirically driven dietary patterns will be derived using reduced rank regression, and their association with Lp(a) will be assessed. For genetic analysis, allele frequencies of the Ethical approval has been obtained from the ethics committees of the Ministry of Health Malaysia (NMRR ID-24-00877-2ID-IIR), Universiti Putra Malaysia (JKEUPM-2024-246), Universiti Teknologi MARA (REC/07/2024-OT/FB/2) and Universiti Malaya Medical Centre (MREC ID NO: 2 02 453-13692). The findings will be disseminated via peer-reviewed journals and conferences. Show less

Breast cancer (BC) is the most prevalent malignancy among women worldwide. Growing evidence highlights the crucial role of circular RNAs (circRNAs) in BC carcinogenesis; however, their underlying mechanisms remain largely unknown. In this study, we identify circCLASP1, which is significantly upregulated in BC tissues (n = 65) and serum samples (n = 61). Its expression correlates with lymph node metastasis, ki67 expression, and tumor size. Receiver operation characteristic (ROC) curve analysis reveals area under the curve (AUC) values of 0.8196 (BC tissues) and 0.8902 (BC serum), respectively. Functionally, circCLASP1 knockdown significantly suppresses BC cell proliferation, migration, and invasion. Mechanistically, circCLASP1 prevents the ubiquitin-mediated degradation of GLI1 protein by facilitating its interaction with CCT2, thereby stabilizing GLI1. Moreover, circCLASP1 enhances the nuclear accumulation of GLI1, leading to increased SNAIL expression and thereby upregulating the expression of CCL2 and CCL5, which in turn promotes macrophage M2 polarization, ultimately resulting in BC progression and subsequent lung metastasis. Further analysis reveals that U2AF2 regulates circCLASP1 biogenesis. Collectively, these findings demonstrate that circCLASP1 promotes BC progression and an immunosuppressive microenvironment via the CCT2/GLI1/SNAIL axis, highlighting its potential as a prognostic biomarker and therapeutic target for BC. Show less

Milk fat globules (MFGs) are a remarkable example of nature's ingenuity. Human milk (HM) carries contains 3-5% fat, 0.8-0.9% protein, 6.9-7.2% carbohydrate calculated as lactose, and 0.2% mineral constituents. Most of these nutrients are carried in these MFGs, which are composed of an energy-rich triacylglycerol (TAG) core surrounded by a triple membrane structure. The membrane contains polar lipids, specialized proteins, glycoproteins, and cholesterol. Each of these bioactive components serves important nutritional, immunological, neurological, and digestive functions. These MFGs are designed to release energy rapidly in the upper gastrointestinal tract and then persist for some time in the gut lumen so that the protective bioactive molecules are conveyed to the colon. These properties may shape the microbial colonization and innate immune properties of the developing gastrointestinal tract. Milk fat globules in milk from humans and ruminants may resemble in structure but there are considerable differences in size, profile, composition, and specific constituents. There are possibilities to not only enhance the nutritional composition in a goal-oriented fashion to correct specific deficiencies in the infant but also to use these fat globules as a nutraceutical in infants who require specific treatments. To mention a few, there might be possibilities in enhancing neurodevelopment, in defense against gastrointestinal and respiratory tract infections, improving insulin sensitivity, treating chronic inflammation, and altering plasma lipids. This review provides an overview of the composition, structure, and biological activities of the various components of the MFGs. We have assimilated research findings from our own laboratory with an extensive review of the literature utilizing key terms in multiple databases including PubMed, EMBASE, and Science Direct. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and PubMed's Medical Subject Heading (MeSH) thesaurus. Show less

The interaction between stromal and tumor cells in tumor microenvironment is a crucial factor in Mantle cell lymphoma (MCL) progression and therapy resistance. We have identified a long non-coding RNA, CERS6-AS1, upregulated in MCL and associated with poor overall survival. CERS6-AS1 expression was elevated in primary MCL within stromal microenvironment and in a subset of MCL cells adhered to stromal layer. These stromal-adhered MCL-subsets exhibited cancer stem cell signatures than suspension counterparts. Mechanistically, we found that downregulating CERS6-AS1 in MCL reduced Fibroblast Growth Factor Receptor-1 (FGFR1), expression attributed to loss of its interaction with RNA-binding protein nucleolin. In addition, using in-silico approach, we have discovered a direct interaction between nucleolin and 5'UTR of FGFR1, thereby regulating FGFR1 transcript stability. We discovered a positive association of CERS6-AS1 with cancer stem cell signatures, and Wnt signaling. Building on these, we explored potential therapeutic strategies where combining nucleolin-targeting agent with FGFR1 inhibition significantly contributed to reversing cancer stem cell signatures and abrogated primary MCL cell growth on stromal layer. These findings provide mechanistic insights into regulatory network involving CERS6-AS1, nucleolin, and FGFR1 axis-associated crosstalk between tumor cells and stromal cell interaction and highlights therapeutic potential of targeting a non-coding RNA in MCL. Show less

Enteric nervous system development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative ENCDCs at the wavefront, but the molecular characteristics of these cells are unknown. ENCDCs from the wavefront and the trailing region were isolated and subjected to RNA-seq. Wavefront-ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. This population of ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike trailing ENCDCs, the wavefront lacked expression of genes related to neuronal or glial maturation. As wavefront ENCDC genes were associated with migration and developmental immaturity, the genes that remain expressed in later progenitor populations may be particularly pertinent to understanding the maintenance of ENCDC progenitor characteristics. Dusp6 expression was specifically upregulated at the wavefront. Inhibiting DUSP6 activity prevented wavefront colonization of the hindgut, and inhibited the migratory ability of post-colonized ENCDCs from midgut and postnatal neurospheres. These effects were reversed by simultaneous inhibition of ERK signaling, indicating that DUSP6-mediated ERK inhibition is required for ENCDC migration in mouse and chick. Show less

The interleukin (IL)-12 family consists of pro- and anti-inflammatory cytokines that are able to signal the activation of host antiviral immunity while preventing over-reactive immune reactions due to active virus replication and viral clearance. Amongst others, IL-12 and IL-23 are produced and released by innate immune cells such as monocytes and macrophages to signal the proliferation of T cells and release of effector cytokines, which subsequently activate host defence against virus infections. Interestingly, the dualities of IL-27 and -35 are evidently shown in the course of virus infections; they regulate the synthesis of cytokines and antiviral molecules, proliferation of T cells, and viral antigen presentation in order to maximize virus clearance by the host immune system. In terms of anti-inflammatory reactions, IL-27 signals the formation of regulatory T cells (Treg) which in turn secrete IL-35 to control the scale of inflammatory response that takes place during virus infections. Given the multitasking of the IL-12 family in regards to the elimination of virus infections, its potential in antiviral therapy is unequivocally important. Thus, this work aims to delve deeper into the antiviral actions of the IL-12 family and their applications in antiviral therapies. Show less

Hypertrophic cardiomyopathy (HCM) is the most prevalent genetic hereditary cardiomyopathy characterized by sudden cardiac death. Mutations in the MYBPC3 gene are often the most prevalent genetic abnormality in HCM with a prevalence ranging from 20.0 to 42.0%. The mutation spectrum is available for different countries, but such studies are lacking in the Asian population including Bangladeshi patients. A cross-sectional descriptive study was conducted for mutation analysis of the whole MYBPC3 gene on a cohort of 75 HCM Bengali Bangladeshi probands through Next Generation Sequencing at the Genetic Research Lab of Bangabandhu Sheikh Mujib Medical University from 2016 to 2019. The structural and functional impact of the mutations was further analyzed by in silico process. We analyzed the data and found 103 variants in 102 locations in the MYBPC3 gene. Variants were identified in both the coding region and the non-coding region. We found one possibly novel variant in the MYBPC3 gene. The findings of this research will help to develop a genetic database of HCM which will help in the early diagnosis and proper management of HCM patients in Bangladesh. One pathogenic splice donor variant (47356592 C >T) was found in the intronic region. Among the variants in the coding region, one missense mutation was pathogenic (NP₋000247.2: p.Asp770Asn) which was found in seven patients and another one is of conflicting interpretations of pathogenicity (NP₋000247.2: p.Ser217Gly) which was found in two patients. We have identified one in-frame deletion (NP₋000247.2: p.Ala433del) that is possible a novel variant responsible for the development of HCM. Show less

Biomarker identification is imperative for invasive breast carcinoma, which is more aggressive and associated with higher mortality and worse prognosis in younger patients (<45 years) than in older patients (>50 years). The current study aimed to investigate angiopoietin-like protein 4 (ANGPTL4) and insulin-like growth factor-1 (IGF-1) protein expression in breast tissue from young patients with breast carcinoma. Immunohistochemical staining was applied in formalin-fixed, paraffin-embedded samples of breast carcinoma tissue from young patients aged <45 years at the time of diagnosis. Both proteins were expressed in the majority of cases. The highest frequency of positive ANGPTL4 and IGF-1 expression was observed in the luminal A subtype, whereas the HER2-overexpression subtype exhibited the lowest expression frequency for both proteins. There was no significant association between ANGPTL4 (p = 0.897) and IGF-1 (p = 0.091) expression and molecular subtypes of breast carcinoma. The histological grade was a significant predictor of ANGPTL4 expression (grade 1 vs. grade 3, adjusted odds ratio = 12.39, p = 0.040). Therefore, ANGPTL-4 and IGF-1 expressions are common in young breast carcinoma tissue. There is a potential use of them as biomarkers in breast carcinoma. Show less

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA. Show less

Concepts surrounding the mechanisms of thrombocytopenia in ITP have shifted from the traditional view of autoantibody mediated platelet destruction to more complex mechanisms in which impaired platelet production, T-cell-mediated effects, and disturbed cytokine profiles play a role. Interleukin 27 (IL-27) plays pleiotropic roles in immunomodulation and autoimmune diseases.We aimed to determine the level of IL-27 in patients with ITP and its relationship to patient and disease characteristics as well as disease chronicity and response to treatment.Sixty childrens with primary immune thrombocytopenia were consequetively enrolled in this study as well as 20 age and sex matched healthy controls.ITP patients had significantly higher levels of IL-27 than controls (770.6 and 373.8 pg/ml, respectively). Patients with acute ITP had the highest levels of IL-27 among patient groups, while patients in remission had the lowest IL-27 levels (860.1and 622.9 pg/ml, respectively). Patients who received IVIG and combined steroids plus IVIG had significantly higher IL-27 levels than others. Patients who received Eltrombopag had significantly lower IL-27 levels than others.IL-27 seems to play a role in pathogenesis of childhood ITP. IL-27 can be used as a predictor for disease occurrence as well as responsiveness to treatment. Show less

This study aimed to identify new genes associated with CRC in patients with normal mismatch repair (MMR) protein expression. Whole-genome sequencing (WGS) was performed in seven early-age-onset Malay CRC patients. Potential germline genetic variants, including single-nucleotide variations and insertions and deletions (indels), were prioritized using functional and predictive algorithms. An average of 3.2 million single-nucleotide variations (SNVs) and over 800 indels were identified. Three potential candidate variants in three genes- This study provides a new spectrum of insights into the potential genes, variants and pathways associated with CRC in Malay patients. Show less

The web-based IceBear software is a versatile tool to monitor the results of crystallization experiments and is designed to facilitate supervisor and student communications. It also records and tracks all relevant information from crystallization setup to PDB deposition in protein crystallography projects. Fully automated data collection is now possible at several synchrotrons, which means that the number of samples tested at the synchrotron is currently increasing rapidly. Therefore, the protein crystallography research communities at the University of Oulu, Weizmann Institute of Science and Diamond Light Source have joined forces to automate the uploading of sample metadata to the synchrotron. In IceBear, each crystal selected for data collection is given a unique sample name and a crystal page is generated. Subsequently, the metadata required for data collection are uploaded directly to the ISPyB synchrotron database by a shipment module, and for each sample a link to the relevant ISPyB page is stored. IceBear allows notes to be made for each sample during cryocooling treatment and during data collection, as well as in later steps of the structure determination. Protocols are also available to aid the recycling of pins, pucks and dewars when the dewar returns from the synchrotron. The IceBear database is organized around projects, and project members can easily access the crystallization and diffraction metadata for each sample, as well as any additional information that has been provided via the notes. The crystal page for each sample connects the crystallization, diffraction and structural information by providing links to the IceBear drop-viewer page and to the ISPyB data-collection page, as well as to the structure deposited in the Protein Data Bank. Show less

Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them. HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7 In vivo results showed a significant ( The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation. Show less

Deoxynivalenol (DON) is a major mycotoxin from the trichothecene family of mycotoxins produced by Fusarium fungi. It can cause a variety of adverse effects on human and farm animal health. Here, we determined the effect of DON on the Class III phosphatidylinositol 3-kinase (PIK3C3)/beclin 1/B cell lymphoma-2 (Bcl-2) pathway in PC12 cells and the relationship between autophagy and apoptosis. The effects of DON were evaluated based on the apoptosis ratio; the typical indicators of autophagy, including cellular morphology, acridine orange- and monodansylcadaverine-labeled vacuoles, green fluorescent protein-microtubule associated protein 1 light chain 3 (LC3) localization, and LC3 immunofluorescence; and the expression of key autophagy-related genes and proteins, that is, PIK3C3, beclin 1, Bcl-2, LC3, and p62. The relationship between autophagy and apoptosis was analyzed by western blot analysis and flow cytometry. DON-induced PC12 cell morphological changes and autophagy significantly. PIK3C3, beclin 1, and LC3 increased in tandem with the DON concentration used; Bcl-2 and p62 expression decreased as DON concentrations increased. Moreover, the PIK3C3/beclin 1/Bcl-2 signaling pathway played a role in DON-induced autophagy. Our findings suggest that DON can induce autophagy by activating the PIK3C3/beclin 1/Bcl-2 signaling pathway and that autophagy may play a positive role in reducing DON-induced apoptosis. Show less

The effects of increasing high-density lipoprotein cholesterol on cardiovascular outcomes remain uncertain. We conducted a meta-analysis to investigate the effects of high-density lipoprotein cholesterol modifiers (niacin, fibrates and cholesteryl ester transfer protein inhibitors) on cardiovascular outcomes. Thirty-one randomized controlled trials (154,601 patients) with a follow-up of 6 months or more and a sample size of 100 or more patients were selected using MEDLINE, EMBASE and CENTRAL database (inception January 2018). High-density lipoprotein cholesterol modifiers had no statistically significant effect on cardiovascular mortality in terms of relative risk (RR) (RR 0.94, 95% confidence interval (CI) 0.89-1.00, P = 0.05, I The use of high-density lipoprotein cholesterol modifying treatments had no significant effect on cardiovascular mortality, stroke or all-cause mortality. The beneficial effect on myocardial infarction was lost when drugs were used with statin therapy. Show less