Inhibitory Effect Research Articles

Role of serpin-25 in prophenoloxidase activation and expression of antimicrobial peptide genes in the silkworm Bombyx mori

Serine protease inhibitors (Serpins) are involved in diverse physiological and developmental processes, constituting one of the largest superfamilies of protease inhibitors. They are widely distributed across various organisms such as plants, animals, prokaryotes, and viruses. In insects, serpins exert their inhibitory effects on serine proteinase cascades, thereby regulating important pathways such as the Toll pathway and prophenoloxidase (proPO) in hemolymph. In this study, we cloned and analyzed the serpin-25 gene in Bombyx mori (Bmserpin-25). Bmserpin-25 mRNA was detected in all examined tissues, with high expression levels observed in the fat body, midgut, and epidermis. Upon injection of B. mori with four different microorganisms, including Gram-positive microbes (Micrococcus luteus), Gram-negative microbes (E. coli), fungi (Beauveria bassiana), and the B. mori nuclear polyhedrosis virus (BmNPV), the significant changes in Bmserpin-25 expression were observed specifically in response to E. coli and BmNPV treatments. Furthermore, the recombinant Bmserpin-25 was successfully expressed in Escherichia coli and purified for subsequent functional analysis. In vitro experiments showed that the recombinant Bmserpin-25 protein inhibited proPO activation but did not affect phenoloxidase activity. Additionally, injection of recombinant Bmserpin-25 protein into B. mori larvae resulted in a significant downregulation of antimicrobial peptide gene expression in the fat body. These findings emphasize the crucial role of serpin-25 in prophenoloxidase activation and the regulation of antimicrobial peptide gene expression in B. mori.

Time-Varying Modeling of Microbial-Induced Calcite Precipitation in Cracked Concrete and Its Inhibitory Effect on Chloride Diffusion

Time-Varying Modeling of Microbial-Induced Calcite Precipitation in Cracked Concrete and Its Inhibitory Effect on Chloride Diffusion

Functional candesartan loaded lipid nanoparticles for the control of diabetes-associated stroke: In vitro and in vivo studies

Diabetes mellitus is a metabolic disease that raises the odds of developing stroke. Candesartan has been used to prevent stroke due to its inhibitory effects on blood pressure, angiogenesis, oxidative damage, and apoptosis. However, oral candesartan has very limited bioavailability and efficacy due to its weak solubility and slow release. The study aimed to develop a nasal formulation of candesartan-loaded liposomes containing ethanol and propylene glycol (CLEP) to improve candesartan's delivery, release, permeation, and efficacy as a potential diabetes-associated stroke treatment. Using design expert software, different CLEP formulations were prepared and evaluated in vitro to identify the optimum formulation, which.The selected optimum formulation composed of 3.3% phospholipid, 10% ethanol, and 15% propylene glycol significantly increased the release and permeation of candesartan relative to free candesartan by a factor of 1.52 and 1.47, respectively. The optimum formulation significantly reduced the infarction after stroke in rats; decreased flexion, spontaneous motor activity, and time spent in the target quadrant by 70%, 64.71%, and 92.31%, respectively, and enhanced grip strength by a ratio of 2.3. Therefore, nasal administration of the CLEP formulation could be a potential diabetes-associated stroke treatment.

Antiviral Compounds to Address Influenza Pandemics: An Update from 2016-2022.

In recent decades, the world has gained experience of the dangerous effects of pandemic events caused by emerging respiratory viruses. In particular, annual epidemics of influenza are responsible for severe illness and deaths. Even if conventional influenza vaccines represent the most effective tool for preventing virus infections, they are not completely effective in patients with severe chronic disease and immunocompromised and new small molecules have emerged to prevent and control the influenza viruses. Thus, the attention of chemists is continuously focused on the synthesis of new antiviral drugs able to interact with the different molecular targets involved in the virus replication cycle. To date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme, hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNA-dependent RNA polymerase have been synthesized using several synthetic strategies comprising the chemical modification of currently used drugs. The best results, in terms of inhibitory activity, are in the nanomolar range and have been obtained from the chemical modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir, Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim of this review is to report, covering the period 2016-2022, the most recent routes related to the synthesis of effective influenza virus inhibitors.

1,3-Diaryl Triazenes Incorporating Disulfonamides Show Both Antiproliferative Activity and Effective Inhibition of Tumor-associated Carbonic Anhydrases IX and XII.

The aim of this study was to synthesize a library of novel di-sulfa drugs containing 1,3- diaryltriazene derivatives TS (1-13) by conjugation of diazonium salts of primary sulfonamides with sulfa drugs to investigate the cytotoxic effect of these new compounds in different cancer types and to determine their inhibitory activity against tumor-associated carbonic anhydrases IX and XII. A carbonic anhydrase inhibitory activity of the obtained compounds was evaluated against four selected human carbonic anhydrase isoforms (hCA I, hCA II, hCA IX and hCA XII) by a stoppedflow CO2 hydrase assay. In addition, in vitro, cytotoxicity studies were applied by using A549 (lung cancer), BEAS-2B (normal lung), MCF-7 (breast cancer), MDA-MB-231 (breast cancer), CRL-4010 (normal breast epithelium), HT-29 (colon cancer), and HCT -116 (colon cancer) cell lines. As a result of the inhibition data, the 4-aminobenzenesulfonamide derivatives were more active than their 3-aminobenzenesulfonamide counterparts. More specifically, compounds TS-1 and TS-2, both of which have primary sulfonamides on both sides of the triazene linker, showed the best inhibitory activity against hCA IX with Ki values of 19.5 and 13.7 nM and also against hCA XII with Ki values of 6.6 and 8.3 nM, respectively. In addition, in vitro cytotoxic activity on the human breast cancer cell line MCF-7 showed that some derivatives of di-sulfa triazenes, such as TS-5 and TS-13, were more active than SLC-0111. With the aim of developing more potent and isoform-selective CA inhibitors, these novel hybrid molecules containing sulfa drugs, triazene linkers, and the classical primary sulfonamide chemotype may be considered an interesting example of effective enzyme inhibitors and important anticancer agents.

Biomimetic “nano-spears” for CAFs-targeting: splintered three “shields” with enhanced cisplatin anti-TNBC efficiency

The treatment dilemma of triple-negative breast cancer (TNBC) revolves around drug resistance and metastasis. Cancer-associated fibroblasts (CAFs) contribute to cisplatin (Cis) resistance and further metastasis in TNBC, making TNBC a difficult-to-treat disease. The dense stromal barrier which restricts drug delivery, invasive phenotype of tumor cells, and immunosuppressive tumor microenvironment (TME) induced by CAFs serve as three “shields” for TNBC against Cis therapy. Here, we designed a silybin-loaded biomimetic nanoparticle coated with anisamide-modified red blood cell membrane (ARm@SNP) as a “nanospear” for CAFs-targeting, which could shatter the “shields” and significantly exhibit inhibitory effect on 4T1 cells in combination with Cis both in vitro and in vivo. The ARm@SNP/Cis elicited 4T1 tumor growth arrest and destroyed three “shields” as follows: disintegrating the stromal barrier by inhibiting blood vessels growth and the expression of fibronectin; decreasing 4T1 cell invasion and metastasis by affecting the TGF-β/Twist/EMT pathway which impeded EMT activation; reversing the immunosuppressive microenvironment by increasing the activity and infiltration of immunocompetent cells. Based on CAFs-targeting, ARm@SNP reversed the resistance of Cis, remodeled the TME and inhibited invasion and metastasis while significantly improving the therapeutic effect of Cis on 4T1 tumor-bearing mice, providing a promising approach for treating intractable TNBC.

1,25-Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling.

Platelet hyperreactivity contributes to the pathogenesis of COVID-19, which is associated with a hypercoagulability state and thrombosis disorder. It has been demonstrated that Vitamin D deficiency is associated with the severity of COVID-19 infection. Vitamin D supplement is widely used as a dietary supplement due to its safety and health benefits. In this study, we investigated the direct effects and underlying mechanisms of 1,25(OH)2D3 on platelet hyperreactivity induced by SRAS-CoV-2 spike protein via Western blot and platelet functional studies in vitro. Firstly, we found that 1,25(OH)2D3 attenuated platelet aggregation and Src-mediated signaling. We further observed that 1,25(OH)2D3 attenuated spike protein-potentiated platelet aggregation in vitro. Mechanistically, 1,25(OH)2D3 attenuated spike protein upregulated-integrin αIIbβ3 outside-in signaling such as platelet spreading and the phosphorylation of β3, c-Src and Syk. Moreover, using PP2, the Src family kinase inhibitor to abolish spike protein-stimulated platelet aggregation and integrin αIIbβ3 outside-in signaling, the combination of PP2 and 1,25(OH)2D3 did not show additive inhibitory effects on spike protein-potentiated platelet aggregation and the phosphorylation of β3, c-Src and Syk. Thus, our data suggest that 1,25(OH)2D3 attenuates platelet aggregation potentiated by spike protein via downregulating integrin αIIbβ3 outside-in signaling.

Morusin Inhibits RANKL-induced Osteoclastogenesis and Ovariectomized Osteoporosis.

Postmenopausal osteoporosis (PMOP) is a classic type of osteoporosis that has gradually become a significant health problem worldwide. There is an urgent need for a safe alternative therapeutic agent considering the poor therapeutic strategies currently available for this disease. The roots and bark of the Morus australis tree (Moraceae) are used to make a traditional Chinese medicine known as "Morusin", and accumulating evidence has demonstrated its multiple activities, such as anti-inflammatory and anti-tumor effects. In this study, we aim to explore the effect of Morusin on mouse osteoclasts and its mechanism. In this study, we explored the inhibitory effects of Morusin on murine osteoclasts in vitro and its mechanism, and the protective effect of Morusin on an ovariectomy (OVX)-induced osteoporosis model in vivo. The results showed that Morusin prevented OVX-induced bone loss and dramatically decreased RANKL-induced osteoclastogenesis. Morusin interfered with RANKL-activated NF- κB, MAPK, and PI3K/AKT signaling pathways. The expression of three master factors that control osteoclast differentiation, c-Fos, NFATc1, and c-Jun, was reduced by Morusin treatment. Collectively, in vitro results indicated that Morusin has a protective effect on OVX-induced bone loss in a mouse model. Our data provide encouraging evidence that Morusin may be an effective treatment for PMOP.

Potentials of TPC and TFC as Free Radical Scavengers and Microbial Growth Inhibitors in Himalayan Endemic Artemisia sieversiana Ehrhl Ex Willd. (Asteraceae) Plant from Northeastern, Pakistan

Background: In various microorganisms, various defense mechanisms have evolved against the commercially available antimicrobial agents with increased resistance. Natural antimi-crobial agents of plant origin are better alternatives when an infectious disease arises due to resistant microbial strains. Here, we have evaluated the efficacy of total phenolics and total flavonoids with antioxidant and antimicrobial potential of Artemisia sieversiana Ehrhl Ex Willd. plant extracted with methanol, ethyl acetate, ethanol, n-hexane, and chloroform using soxhlet procedures Methods: The evaluation of TPC was achieved with Folin-Ciocalteu’s reagent method and quanti-tative estimation of TFC was done with the aluminum chloride colorimetric method. The antioxi-dant activities were estimated using FRSA-DPPH and TAC methods. The inhibitory activities of five solvent extracts of A. sieversiana against 2 gram-positive and 2 gram-negative pathogenic bac-terial strains (B. subtilis, P. aerogenosa, S. aureus, and E. coli) were evaluated using the well dif-fusion technique. Results: The highest percentage yields of A. sieversiana extracts were obtained in ethanol (4.8 g, 12.1%) and methanol (4.01 g, 10%), while minimum extract yield was obtained in n-hexane (0.53 g, 1.34%). Both phenolics and flavonoids were higher in ethanol, methanol, and ethyl acetate ex-tracts while minimal in n-hexane extracts. Ethanol extract has shown maximum (69%) DPPH ac-tivity with a lower IC50 value (181 μg/ml), while the highest IC50 values of 330 and 325μg/ml were recorded for n-hexane and ethyl acetate extracts. The ethyl acetate and chloroform extracts dis-played overall highest TAC values. All the tested extracts of A. sieversiana exhibited variable in-hibitory effects in a dose-dependent manner against the tested bacterial strains with minimum 9.08 ± 0.23 to maximum 21.23 ± 7.04 mm inhibition zones. Methanol and ethyl acetate extracts at 2 to 4 mg/ml showed greater MIC results against P. aeruginosa in comparison to the B. subtilis strain. Conclusion: The extracts of A. sieversiana have been found to be rich in TPC and TFC with re-markable antibacterial and antioxidant efficacies, and the plant extracts could be employed as pos-sible alternatives to synthetic drugs in various nutraceutical and pharmaceutical industries.

Tabersonine Induces the Apoptosis of Human Hepatocellular Carcinoma In vitro and In vivo.

Tabersonine, a natural indole alkaloid derived from Apocynaceae plants, exhibits antiinflammatory and acetylcholinesterase inhibitory activities, among other pharmacological effects. However, its anti-tumor properties and the underlying molecular mechanisms remain underexplored. The present study aims to investigate the anti-tumor effects of tabersonine and its mechanisms in inducing apoptosis in hepatocellular carcinoma. The inhibitory effects of tabersonine on the viability and proliferation of liver cancer cells were evaluated using MTT assay and colony formation assay. AO/EB, Hoechst, and Annexin V-FITC/ PI staining techniques were employed to observe cell damage and apoptosis. JC-1 staining was used to detect changes in mitochondrial membrane potential. Western blot analysis was conducted to study the anti-tumor mechanism of tabersonine on liver cancer cells. Additionally, a xenograft model using mice hepatoma HepG2 cells was established to assess the anti-tumor potency of tabersonine in vivo. Our findings revealed that tabersonine significantly inhibited cell viability and proliferation, inducing apoptosis in liver cancer cells. Treatment with tabersonine inhibited Akt phosphorylation, reduced mitochondrial membrane potential, promoted cytochrome c release from mitochondria to the cytoplasm, and increased the ratio of Bax to Bcl-2. These findings suggested that tabersonine induces apoptosis in liver cancer cells through the mitochondrial pathway. Furthermore, tabersonine treatment activated the death receptor pathway of apoptosis. In vivo studies demonstrated that tabersonine significantly inhibited xenograft tumor growth. Our study is the first to demonstrate that tabersonine induces apoptosis in HepG2 cells through both mitochondrial and death receptor apoptotic pathways, suggesting its potential as a therapeutic agent candidate for hepatic cancer.

Investigating the biomass-specific inhibitory effect of benzalkonium chloride on anaerobic granules: A kinetic approach

Benzalkonium Chloride (BAC), a quaternary ammonium compound commonly used in industrial disinfection processes, was studied for its biomass-specific inhibitory effect on the specific methanogenic activity (SMA) of anaerobic granules. Inhibition batch assays were conducted with varying BAC concentrations (5–40 mg/L), resulting in biomass-dependent inhibition. Considering its surface-active nature, a biomass-specific BAC load was a suitable parameter to determine IC50 values, ranging from 4.3 - 6.1 mg BAC/g VS. For predicting the corresponding biomass-specific inhibition constant in ADM1, the inclusion of an additional adsorption-inhibition term was required for a better validation of results. The model yielded a biomass-specific IC50 of 5.3 mg BAC/g VS. The results encourage a change in perspective on IC50 for surfactants by determining a biomass-specific IC50, particularly in scenarios when surfactants accumulate within anaerobic reactors. Hereby, the reliability and practical relevance of IC50 is increased, driving the development of mitigation strategies.

The Epoxiconazole and Tebuconazole fungicides impair granulosa cells functions partly through the aryl hydrocarbon receptor (AHR) signalling with contrasted effects in obese, normo-weight and polycystic ovarian syndrome (PCOS) patients

Polycystic ovarian syndrome (PCOS), frequently associated to obesity, is the main reproductive disorder in women in age to procreate. Some evidence suggests that pesticides can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). Here, we detected two fungicides, Tebuconazole (Tb) and Epoxiconazole (Epox) in the soils and waters of French area. Our hypothesis is that these two triazoles could be associated to the etiology of PCOS. We used the human KGN cell line and primary human granulosa cells (hGCs) from different group of patients: normal weight non PCOS (NW), normal weight PCOS (PCOS NW), obese (obese) and obese PCOS (PCOS obese). We exposed in vitro these cells to Tb and Epox from 0 up to 10mM for 24 and 48hours and analysed cell viability and steroidogenesis. In hGCs NW, cell viability was reduced from 12.5µM for Tb and 75µM for Epox. In hGCs NW, Epox decreased progesterone (Pg) and estradiol (E2) secretions and inhibited STAR, HSD3B and CYP19A1 mRNA expressions from 25µM and increased AHR mRNA expression from 75µM. Tb exposure also reduced steroid secretion and STAR and CYP19A1 mRNA expressions and increased AHR mRNA expression but at cytotoxic concentrations. Silencing of AHR in KGN cells reduced inhibitory effects of Tb and Epox on steroid secretion. Tb and Epox exposure decreased more steroid secretion in hGCs from obese, PCOS NW and PCOS obese groups than in NW group. Moreover, we found a higher gene expression of AHR within these three groups. Taken together, both Epox and Tb reduced steroidogenesis in hGCs through partly AHR and Tb was more cytotoxic than Epox. These triazoles alter more strongly PCOS and/or obese hGCs suggesting that human with reproductive disorders are more sensitive to triazoles exposure.

Ginseng polysaccharide components attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation

The increasing incidence of obesity has led to widespread attention in the exploration of natural ingredients. Ginseng polysaccharides (PGP), the main components from Panax ginseng, have been reported potential effect to attenuate obesity and regulate lipid metabolism. In this study, we found that PGP inhibited the high-fat diet (HFD)-induced weight gain, fat ratio and fat tissue weight after 8-week administration. Serum and liver lipid analysis showed that PGP decreased the levels of triglyceride and total cholesterol, which was mediated by the inhibition of key genes for fatty acid and cholesterol metabolisms. Metabolomics studies showed that the inhibitory effect of PGP on liver lipid accumulation was significantly correlated with its regulation of citric acid cycle and lysine degradation. PGP regulated the expression of genes related to lysine degradation in both liver tissue and hepatocytes. In addition, PGP reshaped the composition of fecal microbiota at the genus and species levels in obese mice. Spearman's correlation analysis demonstrated that Staphylococcus sciuri, Staphylococcus lentus, and Pseudoflavonifractor sp. An85 may be the potential targets that PGP maintains the abundance of l-lysine against obesity. It concluded that PGP can attenuate obesity and liver lipid accumulation by regulating fecal microbiota and hepatic lysine degradation.

Umbilical Cord Mesenchymal Stem Cells Combined with Fufang Xueshuantong Capsule Attenuate Oxidative Stress and Vascular Lesions in Diabetic Rats by Activating Nrf-2/HO-1 Signaling Pathway

Background:: Macrovascular lesions are the main cause of death and disability in diabetes mellitus, and excessive accumulation of cholesterol and lipids can lead to long-term and repeated damage of vascular endothelial cells. Umbilical cord mesenchymal stem cells (UCMSCs) can attenuate vascular endothelial damage in type 1 diabetic mice, while Fufang Xueshuantong capsule (FXC) has a protective effect on endothelial function; however, whether FXC in combination with UCMSCs can improve T2DM macrovascular lesions as well as its mechanism of action are not clear. Therefore, the aim of this study was to reveal the role of FXC + UCMSCs in T2DM vasculopathy and their potential mechanism in the treatment of T2DM. Methods:: The control and T2DM groups were intragastrically administered with equal amounts of saline, the UCMSCs group was injected with UCMSCs (1×106, resuspended cells with 0.5 mL PBS) in the tail vein, the FXC group was intragastrically administered with 0.58 g/kg FXC, and the UCMSCs + FXC group was injected with UCMSCs (1×106) in the tail vein, followed by FXC (0.58 g/kg), for 8 weeks. Results:: We found that FXC+UCMSCs effectively reduced lipid levels (TG, TC, and LDL-C) and ameliorated aortic lesions in T2DM rats. Meanwhile, Nrf2 and HO-1 expression were upregulated. We demonstrated that inhibition of Nrf-2 expression blocked the inhibitory effect of FXC+UCMSCs-CM on apoptosis and oxidative stress injury. Conclusion:: Our data suggest that FXC+UCMSCs may attenuate oxidative stress injury and macroangiopathy in T2DM by activating the Nrf-2/HO-1 pathway.

Naringenin-Loaded Bovine Serum Albumin Nanoparticles Inhibit Reactive Oxygen Species (ROS) to Prevent Ulcer and Gastric Cancer

Gastric cancer is a malignance of digestive system and effective treatment measures are key to treatment of gastric cancer. In this experiment, we assessed the effect of bovine serum albumin nanoparticle (BASNP)-coated naringenin (NGN) on reactive oxygen species (ROS) in gastric cancer. After preparation of NGN-BASNP and animal model of gastric cancer, rats were administered with NGN-BASNP, ROS agonists and ROS inhibitors, when the model group was set. After one week of intervention, gastric ulcers in rats were measured and Hematoxylin-eosin (HE) staining was performed. Transwell chamber was used to detect cell invasion ability, while 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was detected proliferation ability of gastric cancer cells. Real Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot determined TNF-α mRNA expression and ROS. With about 100 nm diameter of NGN-BASNP nanoparticles, the nanoparticles presented in good shape. Compared with lesions in the model group, NGN-BASNP treatment greatly improved the condition, relieving the ulcer and decreasing the ulcer area (P < 0.05). After adding ROS agonist, inhibitory effect of NGN-BASNP intervention was amplified (P < 0.01) when the ROS level in the NGN-BASNP+ROS agonist group was decreased and TNF-α expression decreased. Moreover, NGN-BASNP effectively suppressed gastric cancer cell proliferation and migration but induced apoptosis. NGN-BASNP inhibited the expression of TNF-α mRNA and ROS level in gastric cancer cells, thereby alleviating gastric ulcer and delaying gastric cancer cell growth.

Inhibitory effects of burdock root tea on plasma ammonia level in mice fed with high-sucrose and low-fibre diet

Inhibitory effects of burdock root tea on plasma ammonia level in mice fed with high-sucrose and low-fibre diet

Setd1A-mediated methylation of h3k4me3 inhibits ferroptosis in non-small cell lung cancer by regulating the WTAPP1/WTAP axis.

SETD1A is upregulated in non-small cell lung cancer (NSCLC) tissues. This study investigated the molecular mechanism of the SETD1A/WTAPP1/WTAP axis in NSCLC. Ferroptosis is a unique cell death mode driven by iron-reliant phospholipid peroxidation, which is regulated by multiple cellular metabolic pathways, including REDOX homeostasis, iron metabolism, mitochondrial activity and metabolism of amino acids, lipids and sugars. Thus, the levels of ferroptosis markers (MDA, SOD, GSH) were measured in vitro, and NSCLC cell behaviors were assessed. SETD1A-mediated H3K4me3 methylation was analyzed. SETD1A-exerted effects on ferroptosis and tumor growth in vivo were verified in nude mouse models. SETD1A was highly expressed in NSCLC cells. Silencing SETD1A suppressed NSCLC cell proliferation and migration, inhibited MDA, and enhanced GPX4, SOD, and GSH levels. SETD1A elevated WTAP expression through WTAPP1 upregulation by mediating H3K4me3 methylation in the WTAPP1 promoter region. WTAPP1 overexpression partly averted the promotional effect of silencing SETD1A on NSCLC cell ferroptosis. WTAP interference abrogated the inhibitory effects of WTAPP1 on NSCLC cell ferroptosis. Silencing SETD1A facilitated ferroptosis and accelerated tumor growth in nude mice through the WTAPP1/WTAP axis. SETD1A amplified WTAP expression through WTAPP1 upregulation by mediating H3K4me3 modification in the WTAPP1 promoter region, thus promoting NSCLC cell proliferation and migration and inhibiting ferroptosis.

A review of the antimicrobial benefits of naturally extracted nanomaterials

Nanotechnology finds immense potential due to the unique characteristics of nanomaterials. Though noble metal nanoparticles, particularly gold and silver nanoparticles possess advanced properties their conventional production methods pose environmental hazards. This paper explores the eco-friendly approaches using natural sources for synthesizing gold and silver nanoparticles. Rose and pomegranate extracts were used to synthesize gold nanoparticles. Evaluation using ultraviolet-visible (UV-Vis) spectroscopy confirmed the nanoparticle formation, and Fourier transform infrared spectroscopy (FT-IR) analysis recognized the presence of plant-derived compounds for stabilizing these particles. In-depth observations of their size and form were provided using electron microscopy, and these findings were aligned with the inferences made from the UV-Vis data. Silver nanoparticles were produced using Ocimum gratissimum leaf extract (OGE), exhibiting dose-dependent antimicrobial effects against bacterial strains. A comparative analysis demonstrated the distinct antibacterial characteristics of silver and gold nanoparticles against several bacterial strains. These nanoparticles demonstrated enhanced inhibitory effects when employed in combination with antibiotics, suggesting the possibility of dealing with antibiotic resistance. The study presents opportunities for producing nanomaterials with minimal impact on the environment and for addressing antibiotic resistance. Further research can enhance the process and find more useful applications as this green synthesis approach can bring about significant improvements in many areas.

Anacardic acid derivatives with significant α-glucosidase inhibitory activity from Syzygium samarangense

Our continuous effort to search for antidiabetic constituents from the leaves of Syzygium samarangense resulted in the isolation of one new anacardic acid derivative, 2-[(Z)-nonadec-14-enyl]-6-hydroxylbenzoic acid (1) along with four known analogues (2−5). The new structure was elucidated by means of extensive spectroscopic data including 1D and 2D NMR along with HRESIMS. The anacardic acid derivatives were isolated from this species for the first time. All compounds exhibited significant inhibitory effect with IC50 value of 0.75−3.60μM against α-glucosidase.

Phytol and α-Bisabolol Synergy Induces Autophagy and Apoptosis in A549 Cells and Additional Molecular Insights through Comprehensive Proteome Analysis via Nano LC-MS/MS.

Non-Small Cell Lung Cancer (NSCLC) is a malignancy with a significant prevalence and aggressive nature, posing a considerable challenge in terms of therapeutic interventions. Autophagy and apoptosis, two intricate cellular processes, are integral to NSCLC pathophysiology, each affecting the other through shared signaling pathways. Phytol (Phy) and α -bisabolol (Bis) have shown promise as potential anticancer agents individually, but their combined effects in NSCLC have not been extensively investigated. The present study was to examine the synergistic impact of Phy and Bis on NSCLC cells, particularly in the context of autophagy modulation, and to elucidate the resulting differential protein expression using LCMS/ MS analysis. The A549 cell lines were subjected to the patented effective concentration of Phy and Bis, and subsequently, the viability of the cells was evaluated utilizing the MTT assay. The present study utilized real-time PCR analysis to assess the expression levels of crucial apoptotic genes, specifically Bcl-2, Bax, and Caspase-9, as well as autophagy-related genes, including Beclin-1, SQSTM1, Ulk1, and LC3B. The confirmation of autophagy marker expression (Beclin-1, LC3B) and the autophagy-regulating protein SQSTM1 was achieved through the utilization of Western blot analysis. Differentially expressed proteins were found using LC-MS/MS analysis. The combination of Phy and Bis demonstrated significant inhibition of NSCLC cell growth, indicating their synergistic effect. Real-time PCR analysis revealed a shift towards apoptosis, with downregulation of Bcl-2 and upregulation of Bax and Caspase-9, suggesting a shift towards apoptosis. Genes associated with autophagy regulation, including Beclin-1, SQSTM1 (p62), Ulk1, and LC3B, showed significant upregulation, indicating potential induction of autophagy. Western blot analysis confirmed increased expression of autophagy markers, such as Beclin-1 and LC3B, while the autophagy-regulating protein SQSTM1 exhibited a significant decrease. LC-MS/MS analysis revealed differential expression of 861 proteins, reflecting the modulation of cellular processes. Protein-protein interaction network analysis highlighted key proteins involved in apoptotic and autophagic pathways, including STOML2, YWHAB, POX2, B2M, CDA, CAPN2, TXN, ECHS1, PEBP1, PFN1, CDC42, TUBB1, HSPB1, PXN, FGF2, and BAG3, emphasizing their crucial roles. Additionally, PANTHER pathway analysis uncovered enriched pathways associated with the differentially expressed proteins, revealing their involvement in a diverse range of biological processes, encompassing cell signaling, metabolism, and cellular stress responses. The combined treatment of Phy and Bis exerts a synergistic inhibitory effect on NSCLC cell growth, mediated through the interplay of apoptosis and autophagy. The differential protein expression observed, along with the identified proteins and enriched pathways, provides valuable insights into the underlying molecular mechanisms. These findings offer a foundation for further exploration of the therapeutic potential of Phy and Bis in the management of NSCLC.