Therapeutic properties of Isoliquiritigenin with molecular modeling studies: Investigation of anti-pancreatic acinar cell tumor and as HMG-CoA reductase inhibitor for treatment of hypercholesterolemia

IntroductionIsoliquiritigenin, one of the components in the root of Glycyrrhiza glabra L., is a member of the flavonoids, which are known to have an anti-tumor activity in vitro and in vivo. HMG-CoA reductase inhibitors, called statins, are used to reduce the risk of heart disease by lowering blood cholesterol levels.Material and methodsHMG-CoA Reductase activity according to the method described by Takahashi S. et al. The structure of human HMG-COA reductase in the resolution of 2.22 Å with X-RAY diffraction method (PDB ID: 1HWK) was obtained from the PDB database.ResultsIn our study, inhibition result of Isoliquiritigenin on HMG-CoA reductase showed lower value IC50 = 193.77±14.85 µg / mL. For a better understanding of biological activities and interactions, the molecular docking study was accomplished. The results of molecular docking revealed that isoliquiritigenin with a docking score of -6.740 has a strong binding affinity to the HMG-COA reductase. Therefore, this compound could be considered as a potential inhibitor for the enzyme. Also, the properties of Isoliquiritigenin against common human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47 were evaluated.ConclusionsThe treated cells with Isoliquiritigenin were assessed by MTT assay for 48h about the cytotoxicity and anti-human pancreatic acinar cell tumor properties on normal (HUVEC) and human pancreatic acinar cell tumor cell lines i.e. 266-6, TGP49, and TGP47. The IC50 of Isoliquiritigenin were 262, 389, and 211 µg/mL against 266-6, TGP49, and TGP47 cell lines, respectively.

An Individualized Algorithm to Predict Mortality in COVID-19 Pneumonia: a Machine Learning Based Study

IntroductionIdentifying SARS-CoV-2 patients at higher risk of mortality is crucial in the management of a pandemic. Artificial intelligence techniques allow to analyze big amount of data to find hidden patterns. We aimed to develop and validate a mortality score at admission for COVID-19 based on high-level machine learning.Material and methodsWe conducted a retrospective cohort study on hospitalized adults COVID-19 patients between March and December 2020. The primary outcome was in-hospital mortality. A machine learning approach on vital parameters, laboratory values, and demographic features was applied to develop different models. Then, a feature importance analysis was performed to reduce the number of variables included in the model, to develop a risk score with good overall performance, that was finally evaluated in terms of discrimination and calibration capabilities. All results underwent cross-validation.Results1,135 consecutive patients (median age 70 years, 64% males) were enrolled, 48 patients were excluded, the cohort was randomly divided in training (760) and test (327). During hospitalization, 251 (22%) patients died. After feature selection, the best performing classifier was random forest (AUC 0.88±0.03). Based on the relative importance of each variable, a pragmatic score was developed, showing good performances (AUC 0.85, ±0.025), and three levels were defined that correlated well with in-hospital mortality.ConclusionsMachine learning techniques were applied in order to develop an accurate in-hospital mortality risk score for COVID-19 based on ten variables. The application of the proposed score has utility in clinical settings to guide the management and prognostication of COVID-19 patients.

Clinical characteristics of patients with subacute thyroidits and factors affecting development hypothyroidism after subacute thyroiditis

IntroductionSubacute thyroiditis (SAT) is typically a self-limiting, inflammatory disease. Patients can experience hypothyroidism during or after an episode. We examined the clinical characteristics based on laboratory and imaging studies in patients with SAT and possible factors contributing to the development of permanent hypothyroidism after SAT.Material and methodsWe retrospectively examined medical records of patients diagnosed with SAT at one medical facility in Turkey. Patients known to have previous thyroid disease, those with <6 months of follow-up after resolution of SAT, and those who lacked sufficient data for analysis were excluded. Of the 283 patients identified 119 met all inclusion criteria. We extracted data on demographics, laboratory tests, neck pain and other symptoms, ultrasonography findings, medication use, and SAT recurrence. We examined the relationships between these variables and development of permanent hypothyroidism.ResultsThe patients were 42 years old on average, and 78% were women. Most patients (70%) described flu-like symptoms before neck pain started; accordingly, 57% had initially visited a specialty other than endocrinology before SAT was diagnosed, and 28% had received antibiotics for misdiagnosed upper respiratory tract infection. In all, 10 patients (8.4%) developed permanent hypothyroidism after SAT. These patients had received steroids significantly longer than did those without permanent hypothyroidism (mean 17.7 vs. 8.9 weeks; P = .021). Development of hypothyroidism was significantly lower among patients with thyrotoxicosis.ConclusionsThe diagnosis of SAT can be challenging. Patients who require longer-term steroids after SAT and who have recurrent SAT should be closely monitored for development of hypothyroidism.

Diagnostic performance of superb microvascular imaging combined with shear-wave elastography in distinguishing invasive ductal carcinoma molecular subtypes

IntroductionTo explore the diagnostic value of combining superb microvascular imaging (SMI), shear-wave elastography (SWE), and Breast Imaging Reporting and Data System (BI-RADS) to distinguish different molecular subtypes of invasive ductal carcinoma (IDC).Material and methodsA total of 239 surgically confirmed IDC masses in 201 patients underwent conventional ultrasound, SMI, and SWE examination, the information such as echo pattern, posterior features, margins, SMI pixels, and hardness of the masses was recorded. According to the St. Gallen standard, breast masses were classified as Luminal A, Luminal B, HER2 overexpression, and triple-negative subtype. We further explored the differences between different molecular subtypes of IDC.ResultsLuminal A subtype had the following characteristics: low histologic grade, posterior acoustic shadowing (p= 0.019), spiculated margins (p<0.001) , and relatively soft. Luminal B subtype was characterized by low histological grade (p <0.0001), posterior acoustic shadowing or indifference, and indistinct margins. HER2 overexpression breast cancers were characterized by high histological grade, enhanced posterior acoustics or indifference, calcifications (p= 0.005), spiculated or indistinct margins, vascularity (p=0.005), and relative stiffness. Triple-negative breast cancers had the characteristics of high histological grade, posterior echogenic enhancement, lack of calcifications, circumscribed or microlobulated margins, low blood flow signals, and stiff tissue (p=0.013).ConclusionsOur study demonstrated the significant differences and trends among the IDC four subtypes by the combined application of SMI, SWE, and BI-RADS lexicon, which are of great significance for early diagnosis, selection of treatment methods, and evaluation of prognosis of IDC.

Hyperoside inhibits lipopolysaccharide-induced mastitis in mice by inactivating the NLRP3 inflammasome

IntroductionThe impact of bovine mastitis on animal husbandry is great huge. It is anincurable an incurable disease mainly characterized by milk and pathological changes in milk and the mammary gland, which causescause reduced yield and quality of milk, but. Unfortunately, the use of antibiotics to combat mastitis affects the production of milk, so it is urgent to find additional therapeutic molecules for mastitis treatment.Material and methodsIn this study, we analyzed the protection provided by hyperoside (HYP) in a model of mastitis in vivo and explored its functional mechanism in mouse mammary epithelial cells (mMECs) by overexpression of NOD-, LRR- and pyrin domain-containing 3 (NLRP3).ResultsOur results showed that HYP at 12.5, 25 and 50 mg/kg prevented the inflammatory response induced in lipopolysaccharide (LPS)-stimulated micemouse mammary glands as well as inflammatory cytokine production, including tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-8. The protection provided by HYP was also correlated with the reduction of NLRP3 signaling pathway protein levels in vivo. However, overexpression of NLRP3 reversed the effects of HYP on the NLRP3 inflammasome, cell viability and inflammatory factor levels in LPS-stimulated mMECs.ConclusionsIn summary, this study showed that HYP inhibited LPS-stimulated symptoms of breast inflammation by regulating expression of inflammatory cytokines and inhibiting the NLRP3 signaling pathway.

Expression of lncRNAs in children with pancreaticobiliary maljunction: functional analysis and potential biomarkers

IntroductionPancreaticobiliary maljunction (PBM) leads to higher rates of complications, including cholangitis,pancreatitis, and malignancies. The present study was to investigat the expression profile of long non-coding RNAs (lncRNAs) and their potential role as biomarkers in children with pancreaticobiliary maljunction.Material and methodsThe differential expression of lncRNAs and mRNAs from 15 pediatric patients with pancreaticobiliary maljunction and 15 control subjects were analyzed using a commercial microarray and validated with qRT-PCR. The potential biological functions of differentially expressed genes were explored based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The ability of potential lncRNA biomarkers to predict pancreaticobiliary maljunction was assessed based on the area under the receiver operating characteristic curve (AUC).ResultsThere were 2915 mRNAs and 173 lncRNAs upregulated, and 2121 mRNAs and 316 lncRNAs downregulated in pancreaticobiliary maljunction cases compared to controls. The enriched Gene Ontology categories associated with differentially expressed mRNAs were extracellular matrix, extracellular region, and kinetochore. The most enriched Kyoto Encyclopedia pathway was protein digestion and absorption, which has been associated with cancer and PI3K-Akt signaling. Analysis of cis- and trans-target genes predicted that a single lncRNA was able to regulate several mRNAs. The qRT-PCR results for NR_110876, NR_132344, XR_946886, and XR_002956345 were consistent with the microarray results, and the difference was statistically significant for NR_132344, XR_946886, and XR_002956345 (p < 0.05). AUC was significant only for XR_946886 (0.837, p < 0.001).ConclusionsOur results implicate lncRNAs in common bile duct pathogenesis in pancreaticobiliary maljunction, and they identify XR_946886 as a potential biomarker for the disease.

Preparation, characterization and investigation of the anti-‎human ovarian cancer of silver nanoparticles green-formulated by Salvia officinalis leaf ‎aqueous extract ‎

IntroductionIn the present study, we decided to prepare and formulate a new chemotherapeutic drug (silver nanoparticles in ‎aqueous medium using Salvia officinalis leaf aqueous extract) for the treatment of human ovarian cancer in the in ‎vitro condition.Material and methodsThe organometallic chemistry tests such as Scanning Electron Microscopy (SEM), UV–Visible Spectroscopy ‎‎(UV-Vis), and Fourier Transformed Infrared Spectroscopy (FT‐IR) were used for characterizing of silver ‎nanoparticles. For investigating the antioxidant potentials of AgNO3, Salvia officinalis aqueous extract, and ‎silver nanoparticles, the DPPH test was used in the presence of butylated hydroxytoluene as the positive ‎control. To survey the cytotoxicity and anti-human ovarian cancer activities of AgNO3, Salvia officinalis ‎aqueous extract, and silver nanoparticles, MTT assay was used on the human ovarian cancer cell lines i.e., Caov-‎‎3‎, SK-OV-3, and PA-1‎. ‎ResultsIn UV-Vis, the clear peak in the wavelength of 421 nm indicated the formation of silver nanoparticles. In FT-IR ‎test, the presence of many antioxidant compounds with related bonds caused the excellent condition for ‎reducing of silver in the silver nanoparticles. The silver nanoparticles inhibited half of the DPPH molecules in ‎the concentration of 251 µg/mL. The best result of anti-human ovarian cancer effects of silver nanoparticles ‎against the above cell lines was observed in the case of the SK-OV-3 cell line. ‎ConclusionsSilver nanoparticles had very low cell viability and anti-human ovarian cancer properties dose-dependently ‎against Caov-3‎, SK-OV-3, and PA-1 cell lines without any cytotoxicity on the normal cell line (HUVECs). ‎

Anti-breast carcinoma effects of green synthesized nickel nanoparticles from Alhagi ‎sparsifolia leaf aqueous extract: A pre-clinical trial study ‎

IntroductionMany nanoparticles have pharmacological and biochemical properties, including antioxidant and anti-‎inflammatory properties, which appear to be involved in anticarcinogenic and antimutagenic activities. In the recent study, nickel nanoparticles were green-synthesized using the Alhagi sparsifolia leaf aqueous ‎extract. ‎Material and methodsThe synthesized Ni nanoparticles‎ were characterized by analytical techniques including SEM, UV-Vis., and FT-‎IR. The nanoparticles were formed in a spherical shape in the average size of 16.19 nm. ‎ResultsIn the antioxidant test, the IC50 of Ni nanoparticles‎ and BHT against DPPH free radicals were 316 and 231 ‎‎µg/mL, respectively. In the cellular and molecular part of the recent study, the treated cells with Ni ‎nanoparticles‎ were assessed by MTT assay for 48h about the cytotoxicity and anti-human breast cancer ‎properties on normal (HUVEC) and breast cancer cell lines i.e. lobular carcinoma of breast (UACC-3133), ‎inflammatory carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453). The viability of ‎malignant breast cell line reduced dose-dependently in the presence of Ni nanoparticles‎. The IC50 of Ni ‎nanoparticles‎ were 477, 548, and 605 µg/mL against lobular carcinoma of breast (UACC-3133), inflammatory ‎carcinoma of the breast (UACC-732), and metastatic carcinoma (MDA-MB-453) cell lines, respectively. ‎ConclusionsAfter clinical study, nickel nanoparticles containing Alhagi sparsifolia leaf aqueous extract may be used to ‎formulate a new chemotherapeutic drug or supplement to treat the several types of human breast cancer. ‎

A comparative experiment on the anti-chronic myeloid leukemia capacities of AgNO3, ‎Scrophularia striata leaf aqueous extract, and silver nanoparticles containing natural ‎compounds ‎

IntroductionIn the current study, silver nanoparticles were prepared and synthesized in aqueous medium using Scrophularia ‎striata leaf extract as stabilizing and reducing agents. Also, we investigated the anti-chronic myeloid leukemia ‎potentials of silver nanoparticles against BV173 (chronic myeloid leukemia in blast crisis), CML-T1 (chronic ‎myeloid leukemia in lymphoid blast crisis), EM-2 (chronic myeloid leukemia in blast crisis; relapse after bone ‎marrow transplantation), and JOSK-M (chronic myeloid leukemia in myelomonocytic) cell lines. ‎Material and methodsSilver nanoparticles were characterized and analyzed using common nanotechnology techniques including UV-‎Vis.‎‏ ‏and FT-IR Spectroscopy, Field Emission-Scanning Electron Microscopy (FE-SEM), and Transmission ‎Electron Microscopy (TEM), and Energy Dispersive X‐ray Spectrometry (EDS). ‎ResultsFT-IR analysis offered antioxidant compounds in the nanoparticles were the sources of reducing power, ‎reducing silver ions to silver nanoparticles. FE-SEM and TEM images revealed a uniform spherical morphology ‎in size of 19.72 nm for the green synthesized nanoparticles. DPPH test revealed similar antioxidant potentials ‎for silver nanoparticles and butylated hydroxytoluene. Silver nanoparticles had very low cell viability and anti-‎chronic myeloid leukemia properties dose-dependently against JOSK-M, EM-2, CML-T1, and BV173 cell lines ‎without any cytotoxicity on the HUVEC cell line. The best result of cytotoxicity properties of silver ‎nanoparticles against the above cell lines was observed in the case of CML-T1 cell line. ‎ConclusionsAfter confirming in the in vivo and clinical trial studies, these nanoparticles can be administrated in humans for ‎the treatment of chronic myeloid leukemia.‎

The Role of Ferroptosis-Related Gene in the Immune Activity and Prognosis of Sepsis

IntroductionSepsis is a leading cause of mortality in intensive care units worldwide. Ferroptosis, a form of regulated cell-death–related iron, has been proven to be altered during sepsis, including increased iron transport and uptake into cells and decreased iron export. A better understanding of the role of ferroptosis in sepsis should expedite the identification of biomarkers for prognostic evaluation and therapeutic interventions.Material and methodsWe used the mRNA expression profiles of sepsis patients from Gene Expression Omnibus (GEO) to analyze the expression level of ferroptosis-related genes and construct molecular subtypes.ResultsTwo distinct ferroptosis patterns were determined, and the overall survival of the two clusters was highly significantly different. Gene comparison analysis was performed on these two groups, and there were a total of 106 differentially expressed genes(DEGs). Pathway enrichment analysis of these genes showed that ferroptosis and immune-related pathways were enriched, suggesting that immune pathways might be critically involved in sepsis. To systematically predict the prognosis of sepsis, we constructed a nomogram model, the calibration plot nomogram showed excellent concordance for the 7-, 14-, and 28-days predicted and actual overall survival probabilities. Finally, the results of bioinformatics analysis were validated in animal and cell modelsConclusionsIn this study, we construct a ferroptosis-related nomogram that can be used for prognostic prediction in sepsis. In addition, we revealed the ferroptosis played a non-negligible role in immune cell infiltration and guiding more effective immunotherapy strategies.