Arbutin attenuates CFA-induced arthritis by modulating expression levels of 5-LOX, NF­κB, IL-17, PGE-2 and TNF-α.

Arbutin, a naturally soluble glycosylated phenol has antioxidant, antimicrobial, antitumor and anti-inflammatory properties. The current exploration appraises the treatment of arthritis by use of Arbutin (25, 50 and 100 mg/kg) orally in CFA-induced rat arthritis model. Body weight changes, paw size, and joint diameter were recorded till the 28th day in the arthritic-induced rats. Hematological, biochemical, oxidative and inflammatory biomarkers were measured through the blood samples of anesthetized rats. Arbutin markedly decreased paw volume, PGE-2, anti-CCP and 5-LOX levels, however, maintained metabolic and hematological balance and prevented weight loss. Radiology and histology changes improved significantly in the ankle joints of rats. Moreover, Arbutin increased gene pointers such as IL-10 and IL-4 while significantly reducing the levels of CRP and WBCs, whereas Hb, platelets and RBCs count markedly raised in post-treatments. Antioxidant levels of SOD, CAT and GSH were improved and MDA level was reduced in treated groups. Rt-PCR investigation showed a significant reduction of the interleukin-1ß, TNF-α, interleukin-6, cyclooxygenase-2, NF-κB and IL-17 and increased expression of gene pointers like IL-4, and IL-10 in treated groups. Assessment of molecular docking revealed a strong binding interaction of Arbutin against 5-LOX, IL-17, TNF-alpha and interleukin-6, cyclooxygenase-2, nuclear factor-κB, IL-4 and iNOS providing a strong association between experimental and theoretical results. As a result, Arbutin has significantly reduced CFA-induced arthritis by modulation of anti-inflammatory cytokines, i.e., IL-10 and IL-4, the pro-inflammatory cytokines panel such as NF-κB, TNF-alpha, IL-1ß, IL-6, PGE-2, 5-LOX and COX-2 and oxidative biomarkers.

Molecular insights of Eucalyptol (1,8-Cineole) as an anti-arthritic agent: in vivo and in silico analysis of IL-17, IL-10, NF-κB, 5-LOX and COX-2.

The monoterpene oxide, Eucalyptol (1,8-Cineole), a primary component of eucalyptus oil, has been evaluated pharmacologically for anti-inflammatory and analgesic activity. Current research aimed to evaluate Eucalyptol's anti-arthritic potential in a Complete Freund's adjuvant induced arthritis that resembles human rheumatoid arthritis. Polyarthritis developed after 0.1 mL CFA injection into the left hind footpad in rats. Oral administration of Eucalyptol at various doses (100, 200 and 400 mg/kg) significantly reduced paw edema, body weight loss, 5-LOX, PGE2 and Anti-CCP levels. Real-time PCR investigation showed significant downregulation of COX-2, TNF-α, NF-κB, IL-17, IL-6, IL-1ß and upregulation of IL-4 and IL-10 in Eucalyptol treated groups. Hemoglobin and RBCs counts significantly increased post-treatment with Eucalyptol while ESR, CRP, WBCs and platelets count significantly decreased. Eucalyptol significantly increased Superoxide Dismutase, Catalase and Glutathione levels compared to CFA-induced arthritic control however, MDA significantly decreased post-treatment. Further, radiographic and histopathological examination of the ankle joints of rodents administered Eucalyptol revealed an improvement in the structure of the joints. Piroxicam was taken as standard. Furthermore, molecular docking findings supported the anti-arthritic efficacy of Eucalyptol exhibited high binding interaction against IL-17, TNF-α, IL-4, IL-10, iNOS NF-κB, 5-LOX, and COX-2. Eucalyptol has reduced the severity of CFA induced arthritis by promoting anti-inflammatory cytokines for example IL-4, IL-10 and by inhibiting pro-inflammatory cytokines such as 5-LOX, COX-2, IL-17, NF-κB, TNF-α, IL-6 and IL-1ß. Therefore, Eucalyptol might be as a potential therapeutic agent because of its pronounced anti-oxidant and anti-arthritic activity.

Study on PTFE superhydrophobic coating modified by IC@dMSNs and its enhanced antibacterial effect.

INTRODUCTION: Vascular catheter-related infections and thrombosis are common and may lead to serious complications after catheterization. Reducing the incidence of such infections has become a significant challenge. OBJECTIVES: This study aims to develop a super hydrophobic nanocomposite drug-loaded vascular catheter that can effectively resist bacterial infections and blood coagulation. METHODS: In this study, a SiO2 nanocoated PTFE (Polytetrafluoroethylene) catheter (PTFE-SiO2) was prepared and further optimized to prepare a SiO2 nanocoated PTFE catheter loaded with imipenem/cilastatin sodium (PTFE-IC@dMSNs). The catheters were characterized for performance, cell compatibility, anticoagulant performance, in vitro and in vivo antibacterial effect and biological safety. RESULTS: PTFE-IC@dMSNs catheter has efficient drug loading performance and drug release rate and has good cell compatibility and anticoagulant effect in vitro. Compared with the PTFE-SiO2 catheter, the inhibition ring of the PTFE-IC@dMSNs catheter against Escherichia coli increased from 3.98 mm2 to 4.56 mm2, and the antibacterial rate increased from about 50.8 % to 56.9 %, with a significant difference (p < 0.05). The antibacterial zone against Staphylococcus aureus increased from 8.63 mm2 to 11.74 mm2, and the antibacterial rate increased from approximately 83.5 % to 89.3 %, showing a significant difference (p < 0.05). PTFE-IC@dMSNs catheter also has good biocompatibility in vivo. Furthermore, the PTFE-IC@dMSNs catheter can reduce the adhesion of blood cells and have excellent anticoagulant properties, and even maintain these properties even with the addition of imipenem/cilastatin sodium. CONCLUSION: Compared with PTFE, PTFE-SiO2 and PTFE-IC@dMSNs catheters have good characterization performance, cell compatibility, and anticoagulant properties. PTFE SiO2 and PTFE-IC@dMSNs catheters have good antibacterial performance and tissue safety against E. coli and S. aureus. Relatively, PTFE-SiO2 and PTFE-IC@dMSNs catheter has better antibacterial properties and histocompatibility and has potential application prospects in anti-bacterial catheter development and anticoagulation.

Consanguineous marriages increase the incidence of recurrent tuberculosis: Evidence from whole exome sequencing.

BACKGROUND: In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases. METHODOLOGY: First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed. RESULTS: The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rß1. Exon 7 of the IL-12Rß1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function. CONCLUSION: Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rß-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rß1, TYK2, or JAK2 in IFN-γ production, warranting further investigation.

Seasonal Variation and Association of Heavy Metals in the Vital Organs of Edible Fishes from the River Jhelum in Punjab, Pakistan.

The toxic effects of heavy metals are drastic, including accumulation. Fish species are important bio-indicators of heavy metal pollution in aquatic bodies. The current study aimed to assess the seasonal variation of heavy metals in the vital organs of mostly consumed fishes in River Jhelum, Pakistan. Samples of fish, including Wallago attu (Malhi), Rita rita (Khagga), and Mystus seenghala (Singhari), were collected from four different sites, i.e., Khushab, Muhammad Wala (M. Wala), 8.R.D and Rasool barrage during summer and winter seasons. Heavy metals such as iron (Fe), lead (Pb), chromium (Cr), cobalt (Co) and Cadmium (Cd) were estimated through acid digestion and spectrometric analysis. Results showed a significantly higher (P < 0.05) amount of these metals in the liver, followed by the kidneys of fish species. There were seasonal variations in the absorption of these metals as well. Cr (11.71) and Fe (58.66) were detected in higher amounts in Khagga which showed the greatest affinity for certain metals in some cases. In contrast, Singhari showed the greatest affinity to other metals in other cases. Comparative analysis revealed that there was a highly significant (P < 0.05) difference for the accumulation of almost all metals in both seasons and summer had the highest concentration of Cd, Pb, Co, Cr and Fe as compared to winter in all four sampling stations in the case of kidney and liver of all the three fishes. Elevated levels of heavy metals were detected in the summer due to increased temperature. Heavy metals found in the River Jhelum may demonstrate that metals can significantly affect the fish species.

Evaluation of the antibacterial activity and protein profiling of Nile tilapia (Oreochromis niloticus) epidermal mucus under different feeds and culture systems (biofloc technology and earthen pond).

The mucus layers of fish serve as the main interface between the organism and the environment. They play an important biological and ecological role. The current study focuses on Nile tilapia epidermal mucus reared under different commercial feeds (coded A and B) and environments (biofloc technology and earthen pond systems). Crude protein levels in feed A and B were 30% and 28%, respectively. Water parameters in all culturing systems were suitable for tilapia throughout the study period. The antimicrobial potency of tilapia (n = 5 from each) epidermal mucus was tested in vitro against human and fish pathogenic strains viz. Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Francisella noatunensis, and Aeromonas hydrophila. To determine the antimicrobial activity, zones of inhibition (ZOI) were measured in millimetres and compared with two antibiotics (chloramphenicol and ciprofloxacin). SDS-PAGE analysis was performed on skin mucus samples of tilapia to determine protein quantity and size (molecular weight). Results of tilapia skin mucus (crude and aqueous) revealed a strong antibacterial effect against all the selected pathogenic strains. However, variation has been observed in the mucus potency and ZOI values between the biofloc and pond tilapia mucus. The crude mucus of tilapia fed on feed A and cultured in the pond exhibited strong antibacterial effects and high ZOI values compared to the mucus of biofloc tilapia, aqueous mucus extracts and positive control chloramphenicol (antibiotic). The SDS-PAGE results showed that the high molecular weight proteins were found in the collected epidermal mucus of BFT-B (240 kDa) and EP-B (230 kDa). Several peptides in fish skin mucus may play a crucial role in the protection of fish against disease-causing pathogens. Thus, it can be utilized in the human and veterinary sectors as an 'antimicrobial' for treating various bacterial infections.

Synthesis, characterization and anti-breast cancer potential of an incensole acetate nanoemulsion from Catharanthus roseus essential oil; in silico, in vitro, and in vivo study.

The characteristics of phytocompounds and essential oils have undergone extensive research in the medical and pharmaceutical sectors due to their extensive usage. In spite of the fact that these molecules are widely used, terpenes, terpenoids, and their derivatives have not yet been well characterized. This study intends to evaluate the prospective activity of incensole acetate (IA), a compound identified and isolated from Catharanthus roseus essential oil by GC/MS analysis and column chromatography, and to analyze the anticancer effect of an IA biosynthesized nanoemulsion against breast cancer. The in silico activity of IA against breast cancer targets was observed by molecular docking, ADMET assessment and molecular dynamics simulations. The IA-mediated nanoformulation exhibited cytotoxicity against breast cancer cell lines at an effective concentration when analyzed by MTT and crystal violet assay. The increased interleukin serum indicators were significantly improved as a result of nanoemulsion treatment in a DMBA-induced rat model. In addition, the anticancer properties of IA biosynthesized nanoemulsion are supported due to their potential effects on biochemical parameters, oxidative stress markers, proinflammatory cytokines, and upon tumor growth profiling in cancer-induced rats.

In Silico and In Vitro Studies of 4-Hydroxycoumarin-Based Heterocyclic Enamines as Potential Anti-Tumor Agents.

The present study reports the one-step synthesis of several 3-formyl-4-hydroxycouramin-derived enamines (4a-4i) in good yields (65-94%). The characterization of the synthesized compounds was carried out via advanced analytical and spectroscopic techniques, such as melting point, electron impact mass spectrometry (EI-MS), 1H-NMR, 13C-NMR, elemental analysis, FTIR, and UV-Visible spectroscopy. The reaction conditions were optimized, and the maximum yield was obtained at 3-4 h of reflux of the reactants, using 2-butanol as a solvent. The potato disc tumor assay was used to assess Agrobacterium tumefaciens-induced tumors to evaluate the anti-tumor activities of compounds (4a-4i), using Vinblastine as a standard drug. The compound 4g showed the lowest IC50 value (1.12 ± 0.2), which is even better than standard Vinblastine (IC50 7.5 ± 0.6). For further insight into their drug actions, an in silico docking of the compounds was also carried out against the CDK-8 protein. The binding energy values of compounds were found to agree with the experimental results. The compounds 4g and 4h showed the best affinities toward protein, with a binding energy value of -6.8 kcal/mol.

Evaluation of Antimicrobial, Anticholinesterase Potential of Indole Derivatives and Unexpectedly Synthesized Novel Benzodiazine: Characterization, DFT and Hirshfeld Charge Analysis.

The pharmacological effectiveness of indoles, benzoxazepines and benzodiazepines initiated our synthesis of indole fused benoxazepine/benzodiazepine heterocycles, along with enhanced biological usefulness of the fused rings. Activated indoles 5, 6 and 7 were synthesized using modified Bischler indole synthesis rearrangement. Indole 5 was substituted with the trichloroacetyl group at the C7 position, yielding 8, exclusively due to the increased nucleophilic character of C7. When trichloroacylated indole 8 was treated with basified ethanol or excess amminia, indole acid 9 and amide 10 were yielded, respectively. Indole amide 10 was expected to give indole fused benoxazepine/benzodiazepine 11a/11b on treatment with alpha halo ester followed by a coupling agent, but when the reaction was tried, an unexpectedly rearranged novel product, 1,3-bezodiazine 12, was obtained. The synthetic compounds were screened for anticholinesterase and antibacterial potential; results showed all products to be very important candidates for both activities, and their potential can be explored further. In addition, 1,3-bezodiazine 12 was explored by DFT studies, Hirshfeld surface charge analysis and structural insight to obrain a good picture of the structure and reactivity of the products for the design of derivatised drugs from the novel compound.

Synthesis, Crystal Structure, DFT Calculations, Hirshfeld Surface Analysis and In Silico Drug-Target Profiling of (R)-2-(2-(1,3-Dioxoisoindolin-2-yl)propanamido)benzoic Acid Methyl Ester.

The work here reflects synthesis, DFT studies, Hirshfeld charge analysis and crystal data exploration of pharmacologically important (R)-2-(2-(1,3-dioxoisoindolin-2-yl)propanamido)benzoic acid methyl ester (5) to understand its properties for further chemical transformations. The methyl anthranilate (2) was produced by the esterification of anthranilic acid in an acidic medium. The phthaloyl-protected alanine (4) was rendered by the fusion of alanine with phthalic anhydride at 150 °C, followed by coupling with (2) furnished isoindole (5). The characterization of products was performed using IR, UV-Vis, NMR and MS. Single-crystal XRD also verified the structure of (5) in which N-H⋯O bonding stabilizes the molecular configuration of (5), resulting in the formation of S(6) hydrogen-bonded loop. The molecules of isoindole (5) are connected in the form of dimers, and the π⋯π stacking interaction between aromatic rings further stabilizes the crystal packing. DFT studies suggest that HOMO is over the substituted aromatic ring, the LUMO is present mainly over the indole side, and nucleophilic and electrophilic corners point out the reactivity of the product (5). In vitro and in silico analysis of (5) shows its potential as an antibacterial agent targeting DNA gyrase and Dihydroorotase from E. coli and tyrosyl-tRNA synthetase and DNA gyrase from Staphylococcus aureus.

Correction: Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors.

[This corrects the article DOI: 10.1039/D2RA07051K.].

In Silico Designing of Thieno[2,3-b]thiophene Core-Based Highly Conjugated, Fused-Ring, Near-Infrared Sensitive Non-fullerene Acceptors for Organic Solar Cells.

The performance of organic solar cells (OSCs) has been improving steadily over the last few years, owing to the optimization of device fabrication, fine-tuning of morphology, and thin-film processing. Thiophene core containing fused ring-type non-fullerene acceptors (NFAs) achieved significant proficiency for highly efficient OSCs. Quantum chemical computations are utilized herein with the motive of suggesting new NIR sensitive, highly efficient low-band gap materials for OSCs. A series of extended conjugated A-π-D-π-A architectured novel fused-ring NFAs (FUIC-1-FUIC-6) containing thieno[2,3-b]thiophene-based donor core are proposed by substituting the end-capped units of synthesized molecule F10IC. Different properties including frontier molecular orbital analysis, density of states analysis, transition density matrix analysis, excitation energy, reorganizational energies of both holes (λh) and electrons (λe), and open-circuit voltage (V oc) were performed employing the density functional theory approach. Charge transfer analysis of the best-designed molecule with the donor complex was analyzed to comprehend the efficiency of novel constructed molecules (FUIC-1-FUIC-6) and compared with the reference. End-caped acceptor alteration induces the reduction of the energy gap between HOMO-LUMO (1.88 eV), tunes the energy levels, longer absorption in the visible and near-infrared regions, larger V oc, smaller reorganizational energies, and binding energy values in designed structures (FUIC-1-FUIC-6) in comparison to reference (FUIC). The designed molecules show the best agreement with the PTBT-T donor polymer blend and cause the highest charge from the HOMO to the LUMO orbital. Our findings predicted that thieno[2,3-b] thiophene-based newly designed molecules would be efficient NFAs with outstanding photovoltaic characteristics and can be used in future applications of OSCs.

Synthesis of an amantadine-based novel Schiff base and its transition metal complexes as potential ALP, α-amylase, and α-glucosidase inhibitors.

A Schiff base ligand HL, (E)-2-((adamantan-1-ylimino)methyl)-6-allylphenol, was synthesized by condensation of amantadine with 3-allyl-2-hydroxybenzaldehyde, followed by the synthesis of its Zn(ii), Co(ii), Cr(iii), and VO(iv) complexes under reflux conditions. The synthesized compounds were comprehensively elucidated by using different spectroscopic and analytical techniques: UV-Vis, 1H and 13C-NMR, FT-IR, ESI-MS, thermal, and single-crystal XRD analysis. The chemical composition of the synthesized compounds was also verified by molar conductance and elemental analysis. An octahedral geometry for Cr(iii) and Co(ii) complexes, tetrahedral for Zn(ii) complex, and square pyramidal geometry have been proposed for VO(iv) complexes. The antidiabetic activities of the synthesized compounds were also evaluated by performing in vitro α-amylase and α-glucosidase inhibition studies. The Co(ii) complex exhibited the highest α-glucosidase inhibitory activity, whereas oxovanadium(iv) and zinc(ii) complexes were also found to be effective against α-amylase. In alkaline phosphatase (ALP) inhibition studies, the HL was found to be inactive, while the complexes showed remarkable enzyme inhibition in the following order: VO > Zn > Co, in a concentration-dependent manner.

Synthesis, characterization, and in vitro anti-cholinesterase screening of novel indole amines.

The present study involved the targeted synthesis and characterization of novel indole amines with anti-acetylcholinesterase profiling. A series of proposed indole amines was virtually screened against human acetylcholinesterase. A few indole amines (23, 24, and 25) showing strong enzyme binding in the in silico studies were synthesized in the laboratory and characterized using spectroscopic (IR, UV, NMR, single crystal XRD) and spectrometric (EIMS, HR-EIMS) methods. The indole amine 23 was crystallized from EtOH and analyzed with single crystal XRD. These ligands interacted with the PAS site in the enzyme, and their binding may disrupt the activity. The in vitro acetylcholinesterase inhibition studies revealed that the IC50 values for indole amines 25 and 24 (4.28 and 4.66 µM, respectively) were comparable to that of galantamine (4.15 µM) and may be studied further as cost-effective acetylcholinesterase inhibitors.

Assessment of Genetic Damage in Coal Miners of Punjab, Pakistan.

Coal miners are continuously exposed to coal mine dust and airborne particulate that act as a potential risk to their health. The present study evaluates the DNA damage in coal miners using the Buccal Micronucleus Cytome (BMCyt) assay. The samples of the blood and buccal epithelial cells of 40 coal miners and 20 control subjects were taken from coal mines of Pail and Padhrar, Pakistan, to establish buccal anomaly frequencies of metal levels in the blood. Besides this, work history and duration hours were also analyzed. Results revealed that micronucleus frequencies positively correlated with the metal concentrations in the miner's blood. The change in the extent of nuclear damage per unit change in the year was 0.170 for micronuclei; however, with addition in each year of working experience, nuclear buds and broken egged nuclei increased by 0.316 and 0.194 units, where each year increases karyolysis by 0.349 units and karyorrhexis by 0.308 units, respectively. An increase in work hours and working years was positively correlated with cytogenetic damage. Nuclear damage in coal miners due to occupational exposure is obvious and increases with increasing work experience. Hence, the Buccal Micronucleus Cytome assay has proved to be an effective cytogenetic biomonitoring tool for assessing genetic and nuclear damage in coal miners.

Evaluation and Association of Heavy Metals in Commonly Used Fish Feed with Metals Concentration in Some Tissues of O. niloticus Cultured in Biofloc Technology and Earthen Pond System.

For successful aquaculture, the primary need is the quality of fish feed, which determines fish flesh quality. The current study was conducted to evaluate the number and concentration of heavy metals in commonly used fish feeds and fish gills, liver, and muscle of biofloc technology and earthen pond systems. Besides this, the correlation between heavy metals in fish feeds with detected metals in the gills, liver, and muscle of fish was also determined. Results revealed that heavy metals concentration, including Cu and Cd, in feed B was significantly greater than in feed A, but the Zn level in feed A was significantly higher than in feed B. Furthermore, the concentration of heavy metals in fish of both aquaculture systems was significantly higher in the liver than in the gills and muscle. The metal concentration in fish feeds and fish edible parts (muscle) was lower than the WHO standard level; however, the amount of Pb was higher in the fish muscle, which is harmful for human consumption. Though the correlation test revealed that all of the metals from the feeds were positively correlated to the metals detected in the fish, but most of the estimated correlation was insignificant. From the current study, it can be concluded that the fish feed producers need to measure feed quality adequately to avoid hazardous contamination by heavy metals in the feed. The ultimate consumer, fish and humans, may, otherwise, be predisposed to assimilate and accumulate these heavy metals.

Assessment and Bioaccumulation of Heavy Metals in Fish Feeds, Water, and Some Tissues of Cyprinus carpio Cultured in Different Environments (Biofloc Technology and Earthen Pond System).

Fish feed quality is the main determinant of fish flesh quality, so it is important for successful aquaculture. The current study determines the concentration of heavy metals in fish feeds (A and B), water, and their bioaccumulation in gills, liver, and muscle of C. carpio cultured in different environments (biofloc technology and earthen pond systems). In addition, the correlation between heavy metals in fish feeds with bioaccumulated metals in fish tissues was also determined. Results revealed that most heavy metal concentration was significantly greater (P < 0.05) in feed B than in feed A but in permissible range, while all the heavy metal concentration was notably higher in earthen ponds than in biofloc technology. Result from the bioaccumulation factor and concentration of the metals showed that heavy metals were highly accumulated in the fish liver followed by gills. The metal concentration in fish feeds and fish edible parts (muscle) was lower than the WHO standard level; however, the amount of Pb was higher in the fish muscle, liver, and gills, which is harmful for human consumption and also for fish health. Though the correlation test revealed that all of the metals from the feeds were positively correlated to the metals in fish tissues, but most of the estimated correlation was significant and linearly correlated. It can be concluded that producers must measure feed quality correctly to avoid heavy metal contamination because it may assimilate and accumulate in the food chain.

In Vivo and In Silico Assessment of the Cardioprotective Effect of Thymus linearis Extract against Ischemic Myocardial Injury.

Myocardial infarction is irreversible cardiac tissue necrosis due to the blockage of one of the arteries. It leads to an insufficient supply of oxygen and nutrients, creating muscular damage in the affected regions. In the present study, aqueous methanolic extract of Thymus linearis was prepared to evaluate its activity against ischemic stress due to free radical production. GC-MS analysis was performed to evaluate the phytochemicals present in the plant extract. A chemical database of 30 compounds was virtually screened against NF-κB, COX2, and MCL, where γ-cadinene, ß-bisabolene, and ß-caryophyllene were found to be the best interacting ligands. To systematically assess cardioprotective activity against ischemia, isoproterenol and doxorubicin were used to induce cardiotoxicity in rats. The prepared extract of T. linearis (100 mg/kg) was given daily to animals for 21 days before injecting isoproterenol (85 mg/kg of animal weight) subcutaneously in two doses on the 20th and 21st days. In the case of doxorubicin, cardiotoxicity was induced in rats by a single injection (15 mg/kg) on the seventh day, and the extract was given to animals for 10 consecutive days. Animals' blood samples were used to monitor cardiac, liver, and other marker enzymes, including LDH, CPK, and AST. Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were also assayed in blood plasma to determine the degree of oxidative stress. H&E staining was performed to evaluate cardioprotection by plant extract, showing significant preventive effects in reducing cardiac injury induced by isoproterenol and doxorubicin.

Efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy to treat multiple myeloma.

OBJECTIVES: This study evaluates the efficacy and safety of plasmapheresis without plasma transfusion tandem with chemotherapy in treating multiple myeloma (MM). METHOD: This retrospective study involves seventy-two patients, newly diagnosed with multiple myeloma, divided into two groups; one with plasmapheresis without plasma transfusion tandem with the chemotherapy group (Trial group), while the second was chemotherapy group (Control group). The levels of Plasma Globulin, ß2-microglobulin, Creatinine, Vascular endothelial growth factor (VEGF), and IL-6 were monitored after plasmapheresis, at initial diagnosis, and after four chemotherapy courses. Overall response rate of groups after four courses of chemotherapy was analyzed, and the adverse events were recorded. RESULTS AND DISCUSSION: The baseline data showed that sixty-seven percent of patients were at the ISS III stage and showed more severe renal insufficiency in the Trial group. The Plasma Globulin, ß2-microglobulin, VEGF and IL-6 levels were significantly different between the two groups during the initial diagnosis. After three times plasmapheresis, Plasma Globulin, ß2-microglobulin, VEGF, and IL-6 were significantly reduced in the plasmapheresis group. The Creatinine levels were also lowered, but the differences were not statistically significant. After four courses of chemotherapy, the levels of VEGF and IL-6 in the two groups were significantly reduced than the initial diagnosis; the differences were statistically considerable. No adverse events were found in the trial group as compared to the control group. CONCLUSION: Plasmapheresis reduces Globulin, ß2-microglobulin, serum VEGF and IL-6 levels in MM, improves renal functions, and releases some patients from dialysis dependence.

Studying in vivo and in vitro effects of a novel polyvinyl benzyl chloride-D-glucaro-1, 4-lactonate polymer-coated bile duct stent for anti-biliary mud deposition.

BACKGROUND: We aim to coat a novel polyvinyl benzyl chloride-D-glucaro-1, 4-lactonate polymer-coated bile duct stent for anti-biliary mud deposition and investigate its in vivo and in vitro impacts. Biliary mud deposition is a leading cause of plastic biliary stent obstruction after its placement. Orally administrated D-glucaro-1, 4-lactonate is a specific competitive inhibitor of ß-glucuronidase that causes biliary mud deposition. METHODS: In this study, the stents coated with polyvinyl benzyl chloride-D-glucaro-1,4-lactonate polymer (PVBC-DGL) were placed in an ex vivo bile duct model perfused with porcine bile and observed every week until completely blocked. Post establishing the model of bile duct stenosis in piglets, stents are observed through endoscopy, hematology, patency time, and pathological changes within 6 months. RESULTS: The 70% PVBC-DGL stents achieved the highest percentage of the inhibitory effect when the drugs were completely released in vitro. Results were obtained from 14 pigs (5: no coating (original), 4: 0% coating, and 5: 70% coating). The overall patency time of the stents was prolonged in all groups; however, the group with 70% coated stents showed a significantly prolonged patency time as compared to no coating (original) and the 0% coating groups in pigs (23.4 ± 1.8 vs 11.2 ± 2.1 w (p = 0.05); 23.4 ± 1.8 vs 10.5 ± 2.5 w (p = 0.05), respectively). CONCLUSION: The stents with 70% PVBC-DGL better prevent and control the deposition of bile mud and prolong the patency time of stent placement in the subject animals and may be proposed for further clinical trials in patients.