Quercetin Protects Against Hypertensive Renal Injury by Attenuating Apoptosis: An Integrated Approach Using Network Pharmacology and RNA Sequencing.

ABSTRACT: Quercetin is known for its antihypertensive effects. However, its role on hypertensive renal injury has not been fully elucidated. In this study, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, and Annexin V staining were used to assess the pathological changes and cell apoptosis in the renal tissues of angiotensin II (Ang II)-infused mice and Ang II-stimulated renal tubular epithelial cell line (NRK-52E). A variety of technologies, including network pharmacology, RNA-sequencing, immunohistochemistry, and Western blotting, were performed to investigate its underlying mechanisms. Network pharmacology analysis identified multiple potential candidate targets (including TP53, Bcl-2, and Bax) and enriched signaling pathways (including apoptosis and p53 signaling pathway). Quercetin treatment significantly alleviated the pathological changes in renal tissues of Ang II-infused mice and reversed 464 differentially expressed transcripts, as well as enriched several signaling pathways, including those related apoptosis and p53 pathway. Furthermore, quercetin treatment significantly inhibited the cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells. In addition, quercetin treatment inhibited the upregulation of p53, Bax, cleaved-caspase-9, and cleaved-caspase-3 protein expression and the downregulation of Bcl-2 protein expression in both renal tissue of Ang II-infused mice and Ang II-stimulated NRK-52E cells. Moreover, the molecular docking results indicated a potential binding interaction between quercetin and TP53. Quercetin treatment significantly attenuated hypertensive renal injury and cell apoptosis in renal tissues of Ang II-infused mice and Ang II-stimulated NRK-52E cells and by targeting p53 may be one of the potential underlying mechanisms.

Development of Pectinase Based Nanocatalyst by Immobilization of Pectinase on Magnetic Iron Oxide Nanoparticles Using Glutaraldehyde as Crosslinking Agent.

To increase its operational stability and ongoing reusability, B. subtilis pectinase was immobilized on iron oxide nanocarrier. Through co-precipitation, magnetic iron oxide nanoparticles were synthesized. Scanning electron microscopy (SEM) and energy dispersive electron microscopy (EDEX) were used to analyze the nanoparticles. Pectinase was immobilized using glutaraldehyde as a crosslinking agent on iron oxide nanocarrier. In comparison to free pectinase, immobilized pectinase demonstrated higher enzymatic activity at a variety of temperatures and pH levels. Immobilization also boosted pectinase's catalytic stability. After 120 h of pre-incubation at 50 °C, immobilized pectinase maintained more than 90% of its initial activity due to the iron oxide nanocarrier, which improved the thermal stability of pectinase at various temperatures. Following 15 repetitions of enzymatic reactions, immobilized pectinase still exhibited 90% of its initial activity. According to the results, pectinase's catalytic capabilities were enhanced by its immobilization on iron oxide nanocarrier, making it economically suitable for industrial use.

Green Synthesis of Low-Glycemic Amylose-Lipid Nanocomposites by High-Speed Homogenization and Formulation into Hydrogel.

In this research, we focused on the production of amylose-lipid nanocomposite material (ALN) through a green synthesis technique utilizing high-speed homogenization. Our aim was to investigate this novel material's distinctive physicochemical features and its potential applications as a low-glycemic gelling and functional food ingredient. The study begins with the formulation of the amylose-lipid nanomaterial from starch and fatty acid complexes, including stearic, palmitic, and lauric acids. Structural analysis reveals the presence of ester carbonyl functionalities, solid matrix structures, partial crystallinities, and remarkable thermal stability within the ALN. Notably, the ALN exhibits a significantly low glycemic index (GI, 40%) and elevated resistance starch (RS) values. The research extends to the formulation of ALN into nanocomposite hydrogels, enabling the evaluation of its anthocyanin absorption capacity. This analysis provides valuable insights into the rheological properties and viscoelastic behavior of the resulting hydrogels. Furthermore, the study investigates anthocyanin encapsulation and retention by ALN-based hydrogels, with a particular focus on the influence of pH and physical cross-link networks on the uptake capacity presenting stearic-acid (SA) hydrogel with the best absorption capacity. In conclusion, the green-synthesized (ALN) shows remarkable functional and structural properties. The produced ALN-based hydrogels are promising materials for a variety of applications, such as medicine administration, food packaging, and other industrial purposes.

In Vitro and In Silico Investigation of Diterpenoid Alkaloids Isolated from Delphinium chitralense.

This study reports the isolation of three new C20 diterpenoid alkaloids, Chitralinine A-C (1-3) from the aerial parts of Delphinium chitralense. Their structures were established on the basis of latest spectral techniques and single crystal X-rays crystallographic studies of chitralinine A described basic skeleton of these compounds. All the isolated Compounds (1-3) showed strong, competitive type inhibition against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in comparison to standard allanzanthane and galanthamine however, chitralinine-C remained the most potent with IC50 value of 11.64 ± 0.08 µM against AChE, and 24.31 ± 0.33 µM against BChE, respectively. The molecular docking reflected a binding free energy of -16.400 K Cal-mol-1 for chitralinine-C, having strong interactions with active site residues, TYR334, ASP72, SER122, and SER200. The overall findings suggest that these new diterpenoid alkaloids could serve as lead drugs against dementia-related diseases including Alzheimer's disease.

Effects of pH and Ionic Salts on the Emulsifying and Rheological Properties of Acorn Protein Isolate.

This study was designed to evaluate the emulsifying and rheological properties of acorn protein isolate (API) in different pH mediums (pH 3, 7 and 9) and in the presence of ionic salts (1 M NaCl and 1 M CaCl2). API shows higher solubility in distilled water at pH 7, while at the same pH, a decrease in solubility was observed for API in the presence of CaCl2 (61.30%). A lower emulsifying activity index (EAI), lower stability index (ESI), larger droplet sizes and slight flocculation were observed for API in the presence of salts at different pHs. Importantly, CaCl2 treated samples showed relevantly higher EAI (252.67 m2/g) and ESI (152.67 min) values at all pH as compared to NaCl (221.76 m2/g), (111.82 min), respectively. A significant increase in interfacial protein concentration (4.61 mg/m2) was observed for emulsion at pH 9 with CaCl2, while the major fractions of API were observed in an interfacial layer after SDS-PAGE analysis. All of the emulsion shows shear thinning behavior (τc > 0 and n < 1), while the highest viscosity was observed for emulsion prepared with CaCl2 at pH 3 (11.03 ± 1.62). In conclusion, API, in the presence of ionic salts at acidic, neutral and basic pH, can produce natural emulsions, which could be substitutes for synthetic surfactants for such formulations.

Impacts of rainfall change on stormwater control and water saving performance of rainwater harvesting systems.

Rainwater harvesting is widely implemented to deal with urban water scarcity and stormwater control issues. In the context of climate change, however, the impacts of rainfall change on rainwater harvesting systems (RHS) are still unknown in many regions. In this study, effects of rainfall change on both water saving and stormwater control performance of RHS across six cities in different climatic zones of Pakistan were investigated and location-specific and adaptive measures to mitigate the negative impacts of rainfall change on RHS were proposed. The commonly defined "dry gets drier, wet gets wetter" rainfall change pattern is not retained in the cities. Water saving performance of RHS is positively affected by increasing trend of rainfall at Khanpur and Peshawar, whereas negatively affected by rainfall decreases at Zhob and Murree. Conversely, increasing trend of rainfall is non-beneficial for stormwater control at Khanpur and Peshawar but rainfall decreases are beneficial at Zhob and Murree. Islamabad and Lahore do not have notable changes in performance of RHS due to the non-significant changing trends in rainfall. The impacts of rainfall change on performance of RHS are dependent on not only the trends and extents of local rainfall change, but also tank sizes and water demands. At Khanpur and Murree, the negative impacts of rainfall change on performance of RHS can be resolved by enlarging tank sizes. At Zhob and Peshawar, however, adjusting contributing areas or water demands should also be considered. Therefore, location-specific and adaptive measures should be adopted for RHS to accommodate rainfall change.

Neuroprotective Potential of Synthetic Mono-Carbonyl Curcumin Analogs Assessed by Molecular Docking Studies.

Cognitive decline in dementia is associated with deficiency of the cholinergic system. In this study, five mono-carbonyl curcumin analogs were synthesized, and on the basis of their promising in vitro anticholinesterase activities, they were further investigated for in vivo neuroprotective and memory enhancing effects in scopolamine-induced amnesia using elevated plus maze (EPM) and novel object recognition (NOR) behavioral mice models. The effects of the synthesized compounds on the cholinergic system involvement in the brain hippocampus and their binding mode in the active site of cholinesterases were also determined. Compound h2 (p < 0.001) and h3 (p < 0.001) significantly inhibited the cholinesterases and reversed the effects of scopolamine by significantly reducing TLT (p < 0.001) in EPM, while (p < 0.001) increased the time exploring the novel object. The % discrimination index (DI) was significantly increased (p < 0.001) in the novel object recognition test. The mechanism of cholinesterase inhibition was further validated through molecular docking study using MOE software. The results obtained from the in vitro, in vivo and ex vivo studies showed that the synthesized curcumin analogs exhibited significantly higher memory-enhancing potential, and h3 could be an effective neuroprotective agent. However, more study is suggested to explore its exact mechanism of action.

α-Glucosidase inhibitory potential and hemolytic evaluation of newly synthesized 3,4,5-trisubstituted-1,2,4-triazole derivatives.

A series of 1, 2, 4-triazole derivatives bearing piperidine moiety has been introduced as new anti-diabetic drug candidates with least cytotoxicity. p-Chlorophenylsulfonyl chloride (1) and ethyl nipecotate (2) were the starting reagents that resulted into corresponding 3,4,5-trisubstituted-1,2,4-triazole (6) through a series of steps. A series of electrophiles, 9a-e, were synthesized by reacting 4-bromobutyryl chloride (7) with differently substituted aromatic amines (8a-e) under basic aqueous medium. Target derivatives, 10a-e, were synthesized by the reaction of compound 6 with N-aryl-4-bromobutanamides (9a-e) in an aprotic solvent. Structures of all the derivatives were verified by spectroscopic analysis using IR, 1H-NMR, 13C-NMR and EIMS. Most of the derivatives revealed moderate to good α-glucosidase inhibitory activity with reference to acarbose. The moderate hemolytic potential demonstrated least toxicity.

5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones: As potent urease inhibitors; synthesis, in vitro screening, and molecular modeling study.

5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones 1-43 were synthesized in a "one-pot" three component reaction and structurally characterized by various spectroscopic techniques such as 1H, 13C NMR, EI-MS, HREI-MS, and IR. All compounds were evaluated for their in vitro urease inhibitory activity. It is worth mentioning that except derivatives 1, 11, 12, and 14, all were found to be more potent than the standard thiourea (IC50 = 21.25 ±â€¯0.15 µM) and showed their urease inhibitory potential in the range of IC50 = 3.70 ±â€¯0.5-20.14 ±â€¯0.1 µM. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules. However, molecular modeling study was performed to confirm the binding interactions of the molecules (ligand) with the active site of enzyme.

Selective dual cholinesterase inhibitors from Aconitum laeve.

New lycoctonine-type dual cholinesterase inhibitor, swatinine-C (1), along with three known norditerpenoid alkaloids, hohenackerine (2), aconorine (5) and lappaconitine (6) and two synthetically known but phytochemically new benzene derivatives, methyl 2-acetamidobenzoate (3) and methyl 4-[2-(methoxycarbonyl)anilino]-4-oxobutanoate (4), was isolated from the roots of A. laeve. Structures of new and known compounds (1-6) were established on the basis of latest spectroscopic techniques and by close comparison with the data available in literature. In vitro, compounds (1-6) were tested against AChE and BChE inhibitory activities. Compounds 1 and 2 showed competitive inhibition against AChE (IC50 = 3.7 µM, 4.53 µM) and BChE (IC50 = 12.23 µM, 9.94 µM), respectively. Compounds 5 and 6 showed promising noncompetitive type of inhibitory profile against AChE (IC50 = 2.51 and 6.13 µM) only. Compounds 3 and 4 showed weak inhibitory profile against both AChE and BChE.

Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum.

Extensive chromatographic separations performed on the basic (pH=8-10) chloroform soluble fraction of Aconitum heterophyllum resulted in the isolation of three new diterpenoid alkaloids, 6ß-Methoxy, 9ß-dihydroxylheteratisine (1), 1α,11,13ß-trihydroxylhetisine (2), 6,15ß-dihydroxylhetisine (3), and the known compounds iso-atisine (4), heteratisine (5), hetisinone (6), 19-epi-isoatisine (7), and atidine (8). Structures of the isolated compounds were established by means of mass and NMR spectroscopy as well as single crystal X-ray crystallography. Compounds 1-8 were screened for their antioxidant and enzyme inhibition activities followed by in silico studies to find out the possible inhibitory mechanism of the tested compounds. This work is the first report demonstrating significant antioxidant and anticholinesterase potentials of diterpenoid alkaloids isolated from a natural source.

Synthesis, enzyme inhibition and molecular docking studies of 1-Arylsulfonyl-4-phenylpiperazine derivatives.

Heterocyclic molecules have been frequently investigated to possess various biological activities during the last few decades. The present work elaborates the synthesis and enzymatic inhibition potentials of a series of sulfonamides. A series of 1-arylsulfonyl-4-Phenylpiperazine (3a-n) geared up by the reaction of 1-phenylpiperazine (1) and different (un)substituted alkyl/arylsulfonyl chlorides (2a-n), under defined pH control using water as a reaction medium. The synthesized molecules were characterized by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. The enzyme inhibition study was carried on α-glucosidase, lipoxygenase (LOX), acetyl cholinesterase (AChE) and butyryl cholinesterase (BChE) enzymes supported by docking simulation studies and the IC50 values rendered a few of the synthesized molecules as moderate inhibitors of these enzymes where, the compound 3e exhibited comparatively better potency against α-glucosidase enzyme. The synthesized compounds showed weak or no inhibition against LOX, AChE and BChE enzymes.

Glomerular diseases outcome at one year in a tertiary care centre.

OBJECTIVES: To determine outcome in primary and secondary glomerular diseases at one year follow up. METHODS: Study design is observational cohort, done in out-patient department, Dow Iinternational Medical College, DUHS. All information gathered on a proforma. All patients with dipstick positive proteinuria and clinical glomerular disease were included in study. Patients with no proteinuria were excluded so were patients with stage 5 CKD. Patients were followed for proteinuria and renal insufficiency at completion of one year follow up. Statistical analysis was done on SPSS version 16. RESULT: Total number of patients who completed one year follow up was 173. Mean age of patients was 51.67+ 10.16 (range 15 to 75 years). Ninety two (53.2%), were males and 81(46.8%) were females, ratio being 1.1: 1.0. Mean weight of our patients was 67.43+ 14.13 Kg, (35 to 107 kg). Commonest cause of glomerular disease in our patient was diabetic nephropathy which was seen in 94.2% patients. Commonest associated problem with glomerular disease was hypertension seen in 66.5% of patients. Four out of 173 patients had stage 5 CKD at end of follow up at one year while quantitativ proteinuria remained same at one year follow up. CONCLUSION: One year follow up is critical for patients with glomerular disease associated with stage 4 CKD as progression to end stage renal failure may be seen within one year in these patients.

Elevated lipoprotein(a) levels: A crucial determinant of cardiovascular disease risk and target for emerging therapies.

Cardiovascular disease (CVD) remains a significant global health challenge despite advancements in prevention and treatment. Elevated Lipoprotein(a) [Lp(a)] levels have emerged as a crucial risk factor for CVD and aortic stenosis, affecting approximately 20 of the global population. Research over the last decade has established Lp(a) as an independent genetic contributor to CVD and aortic stenosis, beginning with Kare Berg's discovery in 1963. This has led to extensive exploration of its molecular structure and pathogenic roles. Despite the unknown physiological function of Lp(a), studies have shed light on its metabolism, genetics, and involvement in atherosclerosis, inflammation, and thrombosis. Epidemiological evidence highlights the link between high Lp(a) levels and increased cardiovascular morbidity and mortality. Newly emerging therapies, including pelacarsen, zerlasiran, olpasiran, muvalaplin, and lepodisiran, show promise in significantly lowering Lp(a) levels, potentially transforming the management of cardiovascular disease. However, further research is essential to assess these novel therapies' long-term efficacy and safety, heralding a new era in cardiovascular disease prevention and treatment and providing hope for at-risk patients.

PEGylated Graphene Oxide as a Nanodrug Delivery Vehicle for Podophyllotoxin (GO/PEG/PTOX) and In Vitro α-Amylase/α-Glucosidase Inhibition Activities.

This study aims to develop a nanodrug delivery system containing podophyllotoxin (PTOX), a known anticancer drug, loaded on graphene oxide (GO). The system's ability to inhibit α-amylase and α-glucosidase enzymes was also investigated. PTOX was isolated from Podophyllum hexandrum roots with a yield of 2.3%. GO, prepared by Hummer's method, was converted into GO-COOH and surface-mobilized using polyethylene glycol (PEG) (1:1) in an aqueous medium to obtain GO-PEG. PTOX was loaded on GO-PEG in a facile manner with a 25% loading ratio. All the samples were characterized using FT-IR spectroscopy, UV/visible spectroscopy, and scanning electron microscopy (SEM). In FT-IR spectral data, GO-PEG-PTOX exhibited a reduction in acidic functionalities and there was an appearance of the ester linkage of PTOX with GO. The UV/visible measurements suggested an increase of absorbance in 290-350 nm regions for GO-PEG, suggesting the successful drug loading on its surface (25%). GO-PEG-PTOX exhibited a rough, aggregated, and scattered type of pattern in SEM with distinct edges and binding of PTOX on its surface. GO-PEG-PTOX remained potent in inhibiting both α-amylase and α-glucosidase with IC50 values of 7 and 5 mg/mL, closer to the IC50 of pure PTOX (5 and 4.5 mg/mL), respectively. Owing to the 25% loading ratio and 50% release within 48 h, our results are much more promising. Additionally, the molecular docking studies confirmed four types of interactions between the active centers of enzymes and PTOX, thus supporting the experimental results. In conclusion, the PTOX-loaded GO nanocomposites are promising α-amylase- and α-glucosidase-inhibitory agents when applied in vitro and have been reported for the first time.

Phytochemical Profiling, Antioxidant, Antimicrobial and Cholinesterase Inhibitory Effects of Essential Oils Isolated from the Leaves of Artemisia scoparia and Artemisia absinthium.

The current studies were focused on the phytochemical profiling of two local wild Artemisia species, Artemisia scoparia and Artemisia absinthium leaves' essential oils, extracted via the hydro distillation method along with evaluation of their antioxidant as well as antimicrobial effects. The constituents of EOs were identified using a combined gas chromatography-mass spectrometric (GC-MS) technique. A total of 25 compounds in A. scoparia essential oil (EOAS) were identified, and 14 compounds with percentage abundance of >1% were tabulated, the major being tocopherol derivatives (47.55%). A total of nine compounds in Artemisia absinthium essential oil (EOAA) were enlisted (% age > 1%), the majority being oleic acid derivatives (41.45%). Strong antioxidant effects were pronounced by the EOAS in DPPH (IC50 = 285 ± 0.82 µg/mL) and in ABTS (IC50 = 295 ± 0.32 µg/mL) free radical scavenging assays. Both the EOs remained potent in inhibiting the growth of bacterial species; Escherichia coli (55−70%) and Shigella flexneri (60−75%) however remained moderately effective against Bacillus subtilis as well as Staphylococcus aureus. Both EOAS and EOAA strongly inhibited the growth of the tested fungal species, especially Aspergillus species (up to 70%). The oils showed anti-cholinesterase potential by inhibiting both Acetylcholinesterase (AChE; IC50 = 30 ± 0.04 µg/mL (EOAS), 32 ± 0.05 µg/mL (EOAA) and Butyrylcholinesterase (BChE; IC50 = 34 ± 0.07 µg/mL (EOAS), 36 ± 0.03 µg/mL (EOAA). In conclusion, the essential oils of A. scoparia and A. absinthium are promising antioxidant, antimicrobial and anticholinergic agents with a different phytochemical composition herein reported for the first time.

Anti-Alzheimer and Antioxidant Effects of Nelumbo nucifera L. Alkaloids, Nuciferine and Norcoclaurine in Alloxan-Induced Diabetic Albino Rats.

The present study is aimed to determine the efficacy and dose response of the nuciferine (1), norcoclaurine (2) and crude extract of Nelumbo nucifera in managements of diabetes, Alzheimer disease and related allergies. Experimentally, alloxan (100 mg/kg body weight (b.w.))-induced diabetic rats (200−250 g) were divided into seven groups (n = 6). Group I: normal control, Group II: diabetic control, Group III: standard treated with glibenclamide and Group lV-VII: treated with methanolic crude extracts (100, 200 mg/kg), nuciferine and norcoclaurine (10 mg/kg b.w.) for 15 days. Different tests were performed, including blood glucose, body weights and antioxidant enzyme assays, i.e., superoxide dismutase (SOD), catalase test (CAT), lipid peroxidation assay (TBARS), glutathione assay (GSH) and acetylcholinesterase (AChE) assay. Nuciferine and norcoclaurine significantly reduced blood glucose (p < 0.05) and restored body weight in diabetic rats. Moreover, nuciferine and norcoclaurine (10 mg/kg) significantly recovered the antioxidant enzymes (SOD, CAT, GPx and GSH) which decreased during induced diabetes. Significant increase in TBARS was also observed in the diabetic group and nuciferine as well as norcoclaurine (10 mg/kg) inhibited the increase in TBARS in diabetic animals (p < 0.05), as compared to glibenclamide. AChE activity was significantly recovered by nuciferine and norcoclaurine (10 mg/kg) both in the blood and brain of the diabetic group (p < 0.05). Nuciferine and norcoclaurine showed potent inhibitory effects against α-glucosidase and α-amylase with IC50, 19.06 ± 0.03, 15.03 ± 0.09 µM and 24.07 ± 0.05, 18.04 ± 0.021 µM, as confirmed by molecular docking studies. This study concludes that nuciferine and norcoclaurine significantly improve memory and could be considered as an effective phytomedicine for diabetes, Alzheimer's disease (AD) and oxidative stress.

Simple kinetic method for assessing catalase activity in biological samples.

A novel kinetic method for measuring catalase activity in biological samples was evaluated. The principle of the current method is based on the oxidation effect of unreacted hydrogen peroxide (H2O2) on pyrogallol red (PGR) using the catalytic effects of molybdenum. The decrease in the absorbance of PGR in the presence of H2O2 with time from 0.5 to 4.5 min was directly proportional to the concentration of H2O2, and, in turn, directly proportional to catalase activity. Erythrocyte lysate homogenates were used to measure catalase activity and the results of the current method were significantly correlated to those of the ammonium peroxovanadate method. The 3.1% within run and 4.7% between run coefficients of variation indicated the high precision of the present novel method. The validation process confirmed that the diagnostic method is appropriate for different types of biological samples. Here, we describe a rapid, relatively easy, and reliable method for measuring catalase activity. The assay could be applied as a diagnostic tool and is suitable in research contexts.•A novel kinetic method for measuring catalase activity in biological samples was evaluated.•The validation process confirmed that the diagnostic method is appropriate for different types of biological samples.•The assay could be applied as a diagnostic tool and is suitable in research contexts.

Huoxin Pill Attenuates Cardiac Inflammation by Suppression of TLR4/NF-κB in Acute Myocardial Ischemia Injury Rats.

Huoxin Pill (HXP), a traditional Chinese medicine, has been prescribed widely in the treatment of coronary heart disease, angina pectoris, and other diseases. However, the possible protective mechanisms of HXP on myocardial ischemia remain unclear. In the current study, we investigated the effects and potential mechanism of HXP on myocardial ischemia and cardiac inflammation and the activation of TLR4/NF-κB pathway. Determination of electrocardiogram, echocardiography, and heart weight index (HWI) indicated that HXP treatment obviously attenuated the elevation of ST-segment, end-diastolic volume, and HWI in the AMI rat model. Enzyme-linked immunosorbent assay (ELISA) demonstrated that Huoxin Pill treatment significantly decreased the levels of CTnT, CK-MB, MDA, IL-6, and TNF-α, while it increased SOD content in serum of the AMI rat model. Moreover, hematoxylin and eosin (HE) and immunohistochemistry (IHC) staining revealed that HXP treatment alleviated pathological change, infiltration of inflammatory cells, levels of IL-6 and TNF-α, and expression of TLR4 and p-NF-κB in cardiac tissues of the AMI rat model. In conclusion, HXP treatment significantly improves cardiac function and attenuates cardiac inflammation by suppressing the activation of TLR4/NF-κB pathway in the ISO-induced AMI rat model. This study provides insights into the potential of HXP on prevention and treatment of AMI.

A Myristoyl-Binding Site in the SH3 Domain Modulates c-Src Membrane Anchoring.

The c-Src oncogene is anchored to the cytoplasmic membrane through its N-terminal myristoylated SH4 domain. This domain is part of an intramolecular fuzzy complex with the SH3 and Unique domains. Here we show that the N-terminal myristoyl group binds to the SH3 domain in the proximity of the RT loop, when Src is not anchored to a lipid membrane. Residues in the so-called Unique Lipid Binding Region modulate this interaction. In the presence of lipids, the myristoyl group is released from the SH3 domain and inserts into the lipid membrane. The fuzzy complex with the SH4 and Unique domains is retained in the membrane-bound form, placing the SH3 domain close to the membrane surface and restricting its orientation. The apparent affinity of myristoylated proteins containing the SH4, Unique, and SH3 domains is modulated by these intramolecular interactions, suggesting a mechanism linking c-Src activation and membrane anchoring.