Safe Agent Research Articles

Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status.

Angiogenesis is the physiological process that results in the formation of new blood vessels develop from pre-existing vasculature and plays a significant role in several physiological and pathological processes. Inhibiting angiogenesis, a crucial mechanism in the growth and metastasis of cancer, has been proposed as a potential anticancer therapy. Different studies showed the beneficial effects of angiogenesis inhibitors either in patients suffering from different cancers, alone or in combination with conventional therapies. Even though there are currently a number of efficient anti-angiogenic drugs, including monoclonal antibodies and kinase inhibitors, the associated toxicity profile and theiraffordability constraints are prompting researchers to search for a safe and affordable angiostatic agent for cancer treatment. Endostatin is one of the endogenous anti-angiogenic candidates that have been extensively pursued for the treatment of cancer, but even over three decades after its discovery, we have not made much advancement in employing it as an anticancer therapeutic despite of its remarkable anti-angiogenic effect with low toxicity profile. A recombinant human endostatin (rh-Es) variant for non-small cell lung cancer was approved by China in 2006 and has since been used effectively. Several other successful clinical trials related to endostatin for various malignancies are either ongoing or have already been completed with promising results. Thus, in this review, we have provided an overview of existing anti-angiogenic drugs developed for cancer therapy, with a summary of tumour angiogenesis in the context of Endostatin, and clinical status of rh-Es in cancer treatment. Furthermore, we briefly discuss the various strategies to improve endostatin features (poor pharmacokinetic properties) for developing rh-Es as a safe and effective agent for cancer treatment.

The Promise of Metal-Doped Iron Oxide Nanoparticles as Antimicrobial Agent.

Antibiotic resistance (AMR) is one of the pressing global public health concerns and projections indicate a potential 10 million fatalities by the year 2050. The decreasing effectiveness of commercially available antibiotics due to the drug resistance phenomenon has spurred research efforts to develop potent and safe antimicrobial agents. Iron oxide nanoparticles (IONPs), especially when doped with metals, have emerged as a promising avenue for combating microbial infections. Like IONPs, the antimicrobial activities of doped-IONPs are also linked to their surface charge, size, and shape. Doping metals on nanoparticles can alter the size and magnetic properties by reducing the energy band gap and combining electronic charges with spins. Furthermore, smaller metal-doped nanoparticles tend to exhibit enhanced antimicrobial activity due to their higher surface-to-volume ratio, facilitating greater interaction with bacterial cells. Moreover, metal doping can also lead to increased charge density in magnetic nanoparticles and thereby elevate reactive oxygen species (ROS) generation. These ROS play a vital role to disrupt bacterial cell membrane, proteins, or nucleic acids. In this review, we compared the antimicrobial activities of different doped-IONPs, elucidated their mechanism(s), and put forth opinions for improved biocompatibility.

Genetically light-enhanced immunotherapy mediated by a fluorinated reduction-sensitive delivery system

The lack of safe and efficient therapeutic agent delivery platforms restricts combined therapy’s effect, and combined cancer therapy’s multi-component delivery effect needs improvement. The novel gene delivery system SS-HPT-F/pMIP-3β-KR was proposed to construct fluorine-containing degradable cationic polymers SS-HPT-F by a mild and simple amino-epoxy ring-opening reaction. By modifying the fluorinated alkyl chain, the delivery efficiency of the plasmid was greatly improved, and the cytoplasmic transport of biomolecules was completed. At the same time, a combination plasmid (MIP-3β-KillerRed) was innovatively designed for the independent expression of immune and photodynamic proteins. Which was efficiently transported to the tumor site by SS-HPT-F. The MIP-3β is expressed as an immune chemokine realize the immune mobilization behavior. The photosensitive protein KillerRed expressed in the tumor killed cancer cells under irradiation and released the exocrine immune factor MIP-3β. The immunogenic cell death (ICD) produced by photodynamic therapy (PDT) also induced the immune response of the organism. The synergistic effect of PDT and MIP-3β mobilized the immune properties of the organism, providing light-enhanced immune combination therapy against malignant tumors. Therefore, in subcutaneous tumor-bearing and metastatic animal models, the carrier tumor growth and mobilize organism produce an immune response without systemic toxicity. This work reports the first efficient gene delivery system that achieves light-enhanced immunotherapy.

Evaluating wound-healing effect of silicon-zinc-boron-containing glycerohydrogel and its effect on mammary glands of high producing dairy cows

Cow’s milk quality, which may deteriorate due to inflammatory processes in the mammary glands, remains one of the important problems of dairy farming and requires effective, safe and affordable therapeutic agents. Nanocomposite silicon-zinc-boron-containing glycerohydrogel (Si-Zn-B-gel) may become a very good solution to the issue. The paper demonstrates wound-healing effect of the glycerohydrogel and confirms its effectiveness for teat hyperkeratosis treatment indairy cows. Results of a rat burn model – based experiment suggest that Si-Zn-B-gel is a promising wound healing agent for topical use. Thus, on Day 9 complete re-epithelialization of the burn surface was observed, with fibrous structures prevailing in the granulation tissue of the dermal layer, on Day 19 a mature scar was formed with a longitudinal alignment of collagen fibers. The production tests conducted inhigh producing dairy cows have demonstrated good therapeutic effect of the Si-Zn-B gel for teat-end hyperkeratosis and confirmed its long-term effect that helps to longer maintain the results achieved during treatment. After a 7-day treatment physiological structure of up to 27.8% teats improved, on Day 14 of the experiment no severe hyperkeratotic lesions were observed and the number of teats that correspond to the physiological norm was 72.2%. Analysis of the data collected shows that the Si-Zn-B-gel is effective for teat-end hyperkeratosis treatment, thus, it prevents mastitis in animals and improves the milk quality.

Nephroprotective peptides of Laennec® in the context of pharmacotherapy for nephro-hepato-metabolic disorders

Background. Renal-hepatic dysfunction, which often occurs in liver dysfunction, requires the use of effective and safe nephroprotective agents. Human placenta hydrolysates (HPH) are hepatoprotectors, but little is known about HPH nephroprotective properties and the molecular mechanisms of their implementation.Objective: identification of potential molecular mechanisms of Laennec® HPH neuroprotective action based on bioinformatic analysis of collected mass spectrometric data.Material and methods. Methods of proteomic analysis of peptide preparations were used. The analysis of Laennec® HPH peptide composition included four stages: drug purification, chromatographic separation of peptides, determination of the multidimensional mass spectrum of peptide fraction and de novo sequencing of the isolated peptides.Results. The study of Laennec® HPH peptide composition allowed to identify 48 peptides that can exhibit nephroprotective effects. It was shown that HPH contains biologically active fragments of nephroprotective adrenomedullins, inhibitor peptides of a number of kinases (FYN, SHH, WNK1/4, SGK1, IRAK4, ROCK1/2) and fibrogenic receptors (PDGFR, TGFB1I1).Conclusion. By inhibiting the listed target proteins, HPH peptides provide nephroprotection through reducing inflammation, anti-stress effects and preventing fibrotic changes in kidney tissue

In Silico Identification of Natural Products and World-Approved Drugs Targeting the KEAP1/NRF2 Pathway Endowed with Potential Antioxidant Profile

In this study, we applied a computer-based protocol to identify novel antioxidant agents that can reduce oxidative stress (OxS), which is one of the main hallmarks of several disorders, including cancer, cardiovascular disease, and neurodegenerative disorders. Accordingly, the identification of novel and safe agents, particularly natural products, could represent a valuable strategy to prevent and slow down the cellular damage caused by OxS. Employing two chemical libraries that were properly prepared and enclosing both natural products and world-approved and investigational drugs, we performed a high-throughput docking campaign to identify potential compounds that were able to target the KEAP1 protein. This protein is the main cellular component, along with NRF2, that is involved in the activation of the antioxidant cellular pathway. Furthermore, several post-search filtering approaches were applied to improve the reliability of the computational protocol, such as the evaluation of ligand binding energies and the assessment of the ADMET profile, to provide a final set of compounds that were evaluated by molecular dynamics studies for their binding stability. By following the screening protocol mentioned above, we identified a few undisclosed natural products and drugs that showed great promise as antioxidant agents. Considering the natural products, isoxanthochymol, gingerenone A, and meranzin hydrate showed the best predicted profile for behaving as antioxidant agents, whereas, among the drugs, nedocromil, zopolrestat, and bempedoic acid could be considered for a repurposing approach to identify possible antioxidant agents. In addition, they showed satisfactory ADMET properties with a safe profile, suggesting possible long-term administration. In conclusion, the identified compounds represent a valuable starting point for the identification of novel, safe, and effective antioxidant agents to be employed in cell-based tests and in vivo studies to properly evaluate their action against OxS and the optimal dosage for exerting antioxidant effects.

Optimizing Anesthetic Practices for Mud Crab: A Comparative Study of Clove Oil, MS-222, Ethanol, and Magnesium Chloride.

Anesthesia serves as an effective method to mitigate the stress response in aquatic animals during aquaculture and product transportation. In this study, we assessed the anesthetic efficacy of clove oil, tricaine methane-sulfonate (MS-222), ethanol, and magnesium chloride by anesthesia duration, recovery time, 24-hour survival rate, and the behavior of mud crabs (Scylla paramamosain). Additionally, the optimal anesthetic concentration for varying body weights of mud crabs was also investigated. The results revealed that clove oil emerged as the optimal anesthetic for mud crabs, with a 24-hour survival rate surpassing those observed in MS-222 and magnesium chloride treatments. Ethanol caused amputation and hyperactivity in mud crabs. Regression analyses between the optimal anesthetic concentration of clove oil and the weight categories of 0.03-27.50 g and 27.50-399.73 g for mud crabs yielded the following equations: y = 0.0036 x3 - 0.1629 x2 + 1.7314 x + 4.085 (R2 = 0.7115) and y = 0.0437 x + 2.9461 (R2 = 0.9549). Clove oil exhibited no significant impact on serum cortisol, glucose, lactate content, aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, or superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in mud crabs across different treatment groups. Anesthesia induced by clove oil in mud crabs resulted in an increase in inhibitory neurotransmitters such as glycine. However, the recovery from anesthesia was associated with elevated levels of the excitatory neurotransmitters L-aspartic acid and glutamate. In conclusion, clove oil proves to be a safe and optimal anesthetic agent for mud crabs, exerting no physiological stress on the species.

Antimicrobial and Antioxidant Activity of Rhamnolipids Biosurfactant is Produced by Pseudomonas aeruginosa

Rhamnolipids are the glycolipid biosurfactant produced by different Pseudomonas species; they show antimicrobial activity and antioxidant. The findings of antimicrobial activity showed the rhamnolipid biosurfactant had an antimicrobial effect against the microorganisms at different concentrations, such as toward Bacillus cereus and Klebsiella pneumoniae, while a lower inhibitory effect toward Staphylococcus aureus and Pseudomonas aeruginosa. The rhamnolipid biosurfactant was shown to have a lower inhibitory effect against fungal strains Candida albicans and Aspergillus niger. The lower minimum inhibitory concentration (MIC) values of rhamnolipid biosurfactant toward the investigated microorganisms were 2 mg/ml for E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa and 3 mg/ml for Staphylococcus aureus, Enterobacter cloacae, Bacillus cereus, Proteus mirabilis, Candida albicans and Aspergillus niger. Rhamnolipid biosurfactant was tested as an antioxidant agent; the results showed 22.7 %, 47.4 %, 79.8 %, 85 % and 91.4 % of antioxidant activity at concentrations 5, 10. 15, 20 and 25 mg/ml, respectively. Cytotoxicity of the rhamnolipid biosurfactant was also examined at different concentrations against human erythrocytes. Hemolysis of the erythrocytes was observed at concentrations 100, 75, 50, 40 and 35 mg/ml, whereas the results exhibited no hemolysis at concentrations 25 and 15 mg/ ml. The study concluded that rhamnolipid biosurfactant showed effective antioxidant activity, no hemolysis at lower concentrations and has a high antimicrobial effect. The rhamnolipid biosurfactant is a suitable and great alternative to be employed as an effective and safe therapeutic agent. Keywords: Antimicrobial; Antioxidant; Cytotoxicity; Rhamnolipid; Pseudomonas aeruginosa

Biocontrol Potential of Streptomyces odonnellii SZF-179 toward Alternaria alternata to Control Pear Black Spot Disease.

Pear black spot disease, caused by Alternaria alternata, is a devastating disease in pears and leads to enormous economic losses worldwide. In this investigation, we isolated a Streptomyces odonnellii SZF-179 from the rhizosphere soil of pear plants in China. Indoor confrontation experiments results showed that both SZF-179 and its aseptic filtrate had excellent inhibitory effects against A. alternata. Afterwards, the main antifungal compound of SZF-179 was identified as polyene, with thermal and pH stability in the environment. A microscopic examination of A. alternata mycelium showed severe morphological abnormalities caused by SZF-179. Protective studies showed that SZF-179 fermentation broth could significantly reduce the diameter of the necrotic lesions on pear leaves by 42.25%. Furthermore, the potential of fermentation broth as a foliar treatment to control black leaf spot was also evaluated. Disease indexes of 'Hosui' and 'Wonwhang' pear plants treated with SZF-179 fermentation broth were lower than that of control plants. Overall, SZF-179 is expected to be developed into a safe and broad-spectrum biocontrol agent. No studies to date have evaluated the utility of S. odonnellii for the control of pear black spot disease; our study fills this research gap. Collectively, our findings provide new insights that will aid the control of pear black spot disease, as well as future studies of S. odonnellii strains.

Prospects for the use of probiotic organisms to develop alternative strategies for disinfection and prevention of infectious diseases

Introduction: An important feature of microorganisms is the ability to adapt to adverse external influences, including the development of multiple antimicrobial resistance, leading to such negative consequences for humans as nosocomial infections, problems with cleaning rooms, medical and industrial equipment. The active use of chemical disinfectants for high-quality disinfection and cleaning has a number of disadvantages, including the risks of pathogens with new mechanisms of resistance to antimicrobial agents. The search for new, effective and safe antimicrobial agents as an alternative to chemical disinfectants is relevant. The use of probiotic strains of microorganisms, including lactic acid bacteria, in this capacity may be a promising area of research.Objective: to analyze the literature data on studies of the potential of probiotic organisms, including lactic acid bacteria, to develop alternative disinfection and prevention strategies.Materials and methods: This review of the subject field has been prepared based on the guiding principles of PRISMA-ScR. SCOPUS, Google Scholar, and RSCI databases were used. The works in Russian and English were considered, for the period 1995-2023.Results: The review included 89 articles exploring the disadvantages of traditional disinfection methods and the search for alternative sanitation strategies. The description of various solutions for the introduction of probiotic purification methods is systematized – using bacteriophages, probiotic microorganisms of R. Bacillus and representatives of lactic acid bacteria as active agents.Conclusions: A system of sanitary measures based on probiotic biodesinfectants, including lactic acid bacteria, can be included among the tools for countering pathogens, including their biofilms and forms with multidrug resistance. The introduction of a probiotic hygienic cleaning system, without having a negative impact on the environment, can increase the effectiveness of traditional hygienic preventive measures both in medical institutions and in production.

Chemotherapeutic Activity of Imidazolium-Supported Pd(II) o-Vanillylidene Diaminocyclohexane Complexes Immobilized in Nanolipid as Inhibitors for HER2/neu and FGFR2/FGF2 Axis Overexpression in Breast Cancer Cells.

Two bis-(imidazolium-vanillylidene)-(R,R)-diaminocyclohexane ligands (H2(VAN)2dach, H2L1,2) and their Pd(II) complexes (PdL1 and PdL2) were successfully synthesized and structurally characterized using microanalytical and spectral methods. Subsequently, to target the development of new effective and safe anti-breast cancer chemotherapeutic agents, these complexes were encapsulated by lipid nanoparticles (LNPs) to formulate (PdL1LNP and PdL2LNP), which are physicochemically and morphologically characterized. PdL1LNP and PdL2LNP significantly cause DNA fragmentation in MCF-7 cells, while trastuzumab has a 10% damaging activity. Additionally, the encapsulated Pd1,2LNPs complexes activated the apoptotic mechanisms through the upregulated P53 with p < 0.001 and p < 0.05, respectively. The apoptotic activity may be triggered through the activity mechanism of the Pd1,2LNPs in the inhibitory actions against the FGFR2/FGF2 axis on the gene level with p < 0.001 and the Her2/neu with p < 0.05 and p < 0.01. All these aspects have triggered the activity of the PdL1LNP and PdL2LNP to downregulate TGFβ1 by p < 0.01 for both complexes. In conclusion, LNP-encapsulated Pd(II) complexes can be employed as anti-cancer drugs with additional benefits in regulating the signal mechanisms of the apoptotic mechanisms among breast cancer cells with chemotherapeutic-safe actions.

1,3-Substituted β-Carboline Derivatives as Potent Chemotherapy for the Treatment of Cystic Echinococcosis.

Echinococcosis is a global public health issue that generally occurs in areas with developed animal husbandry. In search of safe and effective therapeutic agents against echinococcosis, we designed and synthesized new 1,3-substituted β-carboline derivatives based on harmine. Among them, compounds 1a, 1c, and 1e displayed potent inhibitory activity against Echinococcus granulosus in vitro, significantly better than albendazole and harmine. The morphological detection revealed that 1a, 1c, and 1e significantly changed the ultrastructure of Echinococcus granulosus protoscolices (PSCs). Furthermore, pharmacokinetic studies suggested that 1a possessed a better metabolic property. Encouragingly, 1a exhibited a highest cyst inhibition rate as 76.8% in vivo and did not display neurotoxicity in mice. Further mechanistic research illustrated that 1a has the potential to induce autophagy in PSCs, which may be responsible for the therapeutic effect of the drugs. Together, 1a could be a promising therapeutic agent against echinococcosis, warranting further study.

Hafnium (Hf)-Chelating Porphyrin-Decorated Gold Nanosensitizers for Enhanced Radio-Radiodynamic Therapy of Colon Carcinoma.

X-ray-induced radiodynamic therapy (RDT) that can significantly reduce radiation dose with an improved anticancer effect has emerged as an attractive and promising therapeutic modality for tumors. However, it is highly significant to develop safe and efficient radiosensitizing agents for tumor radiation therapy. Herein, we present a smart nanotheranostic system FA-Au-CH that consists of gold nanoradiosensitizers, photosensitizer chlorin e6 (Ce6), and folic acid (FA) as a folate-receptor-targeting ligand for improved tumor specificity. FA-Au-CH nanoparticles have been demonstrated to be able to simultaneously serve as radiosensitizers and RDT agents for enhanced computed tomography (CT) imaging-guided radiotherapy (RT) of colon carcinoma, owing to the strong X-ray attenuation capability of high-Z elements Au and Hf, as well as the characteristics of Hf that can transfer radiation energy to Ce6 to generate ROS from Ce6 under X-ray irradiation. The integration of RT and RDT in this study demonstrates great efficacy and offers a promising therapeutic modality for the treatment of malignant tumors.

Hyposidra talaca NPV (HytaNPV): a potential baculovirus for efficient control of the black inch worm, Hyposidra talaca Walker (Lepidoptera: Geometridae), a major pest of tea Camellia sinensis (Ericales: Theaceae (L.) O. Kuntze)

BackgroundThe black inch worm (BIW), Hyposidra talaca Walker (Lepidoptera: Geometridae), is a pest that defoliates tea leaves in India, posing a significant threat to the tea industry. Nucleopolyhedrovirus (NPV) is capable of infecting larvae of this species, which has raised the possibility of its use as a biocontrol agent.ResultsRearing larvae in a semi-synthetic artificial diet produced healthy adults, which is sufficient for mass culture of H. talaca to support one of the IPM components using baculovirus. In artificial diets, the NPV was evaluated for its insecticidal activity against H. talaca. The bioassay findings of inoculated H. talaca nucleopolyhedrovirus virus (HytaNPV) at various concentrations showed that it was effective in killing the BIW. Purified polyhedral inclusion bodies (PIBs) were estimated to a concentration of 1 × 1010 PIBs per ml by mixing with water, and various concentrations of 0.25, 0.5, 1, 2, 5, 7.5, 10 ml/l were evaluated against BIW. Both laboratory and field studies revealed that HytaNPV is an eco-friendly and ecologically safe agent for controlling BIW. Besides no residue was estimated in made tea after the seventh day of exposure, and it is nontoxic to non-target species.ConclusionIt was found that NPV is environmentally beneficial for the control of pests on tea plants and in production of pesticide-free tea. Tea ecosystems can reduce their reliance on conventional insecticides by using HytaNPV as an alternative bio-insecticide.

Efficacy and safety of tenofovir alafenamide in patients with chronic hepatitis B exhibiting suboptimal response to entecavir.

Entecavir (ETV) is a potent and safe antiviral agent for patients with chronic hepatitis B (CHB); however, some patients may exhibit suboptimal response or resistance to ETV. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with improved pharmacokinetics and reduced renal and bone toxicity compared with tenofovir disoproxil fumarate. To evaluate the efficacy and safety of switching from ETV to TAF in patients with CHB exhibiting suboptimal response to ETV. A total of 60 patients with CHB who had been treated with ETV for at least 12 mo and had persistent or recurrent viremia [Hepatitis B virus (HBV) DNA ≥ 20 IU/mL] or partial virologic response (HBV DNA < 20 IU/mL, but detectable) were enrolled in the study. The patients were randomly assigned to either continue ETV (0.5 mg) daily or switch to TAF (25 mg) daily for 48 wk. The primary endpoint was the proportion of patients who achieved a virologic response (HBV DNA level < 20 IU/mL) at week 48. Secondary endpoints included changes in serum alanine aminotransferase (ALT), hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and anti-HBe levels, and renal and bone safety parameters. At week 48, the proportion of patients who achieved a virologic response was significantly higher in the TAF group than in the ETV group (93.3% vs 66.7%, P = 0.012). The mean reduction in HBV DNA from baseline was also significantly greater in the TAF group than in the ETV group (-3.8 vs -2.4 Log10 IU/mL, P < 0.001). The rates of ALT normalization, HBeAg loss, HBeAg seroconversion, and HBsAg loss were not found to significantly differ between the two groups. None of the patients developed genotypic resistance to ETV or TAF. Both drugs were well tolerated, with no serious adverse events or discontinuations caused by adverse events. No significant changes were observed in the estimated glomerular filtration rate, serum creatinine level, or urine protein-to-creatinine ratio in either group. The TAF group had a significantly lower decrease in bone mineral density at the lumbar spine and hip than the ETV group (-0.8% vs -2.1%, P = 0.004; -0.6% vs -1.8%, P = 0.007, respectively). Switching from ETV to TAF is effective and safe for patients with CHB exhibiting a suboptimal response to ETV and may prevent further viral resistance and reduce renal and bone toxicity.

Boric Acid-Functionalized Carbon Dots as a High-Performance Antibacterial Agent against Escherichia coli.

Bacterial infections and antibiotic abuse are a global threat to human health. In recent years, there has been a boom in research on antimicrobial agents with low toxicity and efficient nanomaterials. Boric acid-functionalized carbon dots (B-CDs) with negative surface charge were synthesized by the hydrothermal method. Covalent bonds were formed between the boric acid groups and the cis-diol groups of the polysaccharide in the bacterial cell wall, and numerous B-CDs were trapped on the bacterial surface. In the experiments of antibacterial activity, B-CDs presented strong bactericidal activity against Escherichia coli (E. coli) with a minimum bactericidal concentration of 12.5 μg/mL. The antibacterial mechanism suggested that B-CDs entered the cell interior by diffusion and posed significant damage to the double helix structure of E. coli DNA. Furthermore, B-CDs exhibited low toxicity. The results demonstrated that the novel antimicrobial B-CDs not only fought against E. coli infection and antibiotic misuse but also provided new ideas for safe and effective antimicrobial agents of carbon nanomaterials.

Anti-Microbial Activity and GC-MS Profiling of Leaves Extracts of Hyptis suaveolens: In vitro and In silico Studies

Anti-microbial resistance turned into the main source of death universally, bringing about a critical requirement for the development of new, safe, and potent anti-microbial agents. Compounds retrieved from plants can be a fundamental source of new antibiotics. The Hyptis suaveolens plant is rich in anti-microbial phytochemicals. Here, we used the gas chromatography-mass spectrometry (GC-MS) approach for the quantitative and qualitative identification of bioactive compounds in the methanolic extract of Hyptis suaveolens leaves. Subsequently, anti-microbial activity, pharmacokinetics, and toxicological properties were predicted using in silico tools. The methanolic extract of Hyptis suaveolens leaves was found to have anti-microbial activity against all pathogenic strains (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Candida albicans). The methanolic crude extract shows the highest zone of inhibition against Candida albicans, Bacillus subtilis, and Staphylococcus aureus. The phytochemical, TLC, UV-VIS, and FTIR analyses represented the maximum absorption and functional groups of phytochemicals. GC-MS analysis revealed the presence of 34 secondary metabolites. In silico studies revealed that megastigmatrienone was the most active compound on dihydrofolate reductase (DHFR) in different organisms. It showed the best minimum binding energy (-6.8 kcal/mol). The methanolic crude extract of Hyptis suaveolens leaves showed powerful anti-microbial action against five types of bacteria and one fungus. Megastigmatrienone was the most bioactive compound, and it passed Lipinski's rule of 5 to determine the drug-likeness properties. Therefore, the compound Megastigmatrienone is further subjected to animal testing and clinical trials for its use as an anti-microbial agent with commercial values.

Vasoinhibin's Apoptotic, Inflammatory, and Fibrinolytic Actions Are in a Motif Different From Its Antiangiogenic HGR Motif.

Vasoinhibin, a proteolytic fragment of the hormone prolactin, inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells, and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48 (H46-G47-R48), allowing the development of potent, orally active, HGR-containing vasoinhibin analogues for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed. Here, we report that HGR-containing analogues are devoid of these properties. Instead, the incubation of human umbilical vein endothelial cells with oligopeptides containing the sequence HNLSSEM, corresponding to residues 30 to 36 of vasoinhibin, induced apoptosis, nuclear translocation of NF-κB, expression of genes encoding leukocyte adhesion molecules (VCAM1 and ICAM1) and proinflammatory cytokines (IL1B, IL6, and TNF), and adhesion of peripheral blood leukocytes. Also, intravenous or intra-articular injection of HNLSSEM-containing oligopeptides induced the expression of Vcam1, Icam1, Il1b, Il6, and Tnf in the lung, liver, kidney, eye, and joints of mice and, like vasoinhibin, these oligopeptides promoted the lysis of plasma fibrin clots by binding to plasminogen activator inhibitor-1 (PAI-1). Moreover, the inhibition of PAI-1, urokinase plasminogen activator receptor, or NF-κB prevented the apoptotic and inflammatory actions. In conclusion, the functional properties of vasoinhibin are segregated into 2 different structural determinants. Because apoptotic, inflammatory, and fibrinolytic actions may be undesirable for antiangiogenic therapy, HGR-containing vasoinhibin analogues stand as selective and safe agents for targeting pathological angiogenesis.

Modulation of the properties of starch gels by a one-step extrusion modification method based on Ca2+-citric acid synergistic crosslinking

Citric acid (CA) is a green and safe food-grade crosslinking agent for starch, but its high crosslinking temperature limits its application. In this study, a “one-step” extrusion modification method based on Ca2+-esterification synergistic crosslinking was proposed for the preparation of high gel performance crosslinked starch at low temperatures (90 °C). The linear and nonlinear rheological properties of crosslinked starch were comprehensively characterized, and the enhancement effect of synergistic crosslinking reactions on starch gel properties was quantitatively studied. The results show that the elastic modulus of the synergistically crosslinked starch (SC-0.5Ca2+, G' = 3116 ± 36) was significantly increased by 879 % compared to the elastic modulus of starch without synergistically crosslinked modification (SC, G' = 318 ± 9). The elastic modulus of starch gels can be adjusted by changing the ion concentration. Nonlinear rheological Lissajous curve analysis results show that the synergistic crosslinked gel system has a stronger anti-deformation ability. In addition, the honeycomb porous structure and smaller pore size distribution of the synergistic crosslinked gels were characterized using scanning SEM. The XPS, FTIR and XRD results suggest that the synergistic crosslinking enhancement effect may involve various molecular forces such as electrostatic attraction, hydrogen bonding and ester bonding.

Remimazolam besylate versus propofol for deep sedation in critically ill patients: a randomized pilot study

ObjectiveTo compare the efficacy and safety of remimazolam besylate and propofol for deep sedation in critically ill patients.MethodsIn this single-center, prospective, randomized, controlled pilot study, patients in the intensive care unit (ICU) requiring deep sedation were randomized to receive remimazolam besylate or propofol intravenously. Deep sedation was defined as a Richmond Agitation and Sedation Scale (RASS) score of − 4 or − 5. Sedation depth was monitored using RASS and Narcotrend Index (NI). The primary outcome was the percentage of time within the target sedation range without rescue sedation. The secondary outcomes included ventilator-free hours within 7 days, successful extubation, length of ICU stay, and 28-day mortality. Adverse events during the interventional period were also recorded.ResultsThirty patients were assigned to each group. The median (IQR) RASS score was − 5.0 (− 5.0, − 4.0), and the median (IQR) NI value was 29.0 (21.0, 37.0) during the intervention period. Target RASS was reached a median of 100% of the sedation time in the two groups. No significant differences were observed in ventilator-free hours within 7 days, successful extubation, length of ICU stay, or 28-day mortality among groups. Hypotension occurred in 16 (53.3%) patients of remimazolam group and 18 (60.0%) patients of propofol group (p > 0.05). No patient experienced bradycardia.ConclusionsRemimazolam besylate appears to be an effective and safe agent for short-term deep sedation in critically ill patients. Our findings warrant large sample-sized randomized clinical trials.