Strong Inhibitory Effect Research Articles

TPCA-1 compound, inhibiting testis-specific serine/threonine protein kinase 3 for potential male sterile in Bombyx mori.

Protein kinases are a type of transferase enzyme that catalyze the phosphorylation of protein substrates, including receptor proteins. Testis-specific serine/threonine kinases (TSSKs) are a highly conserved group of protein kinases found in various organisms. They play an essential role in male reproduction by influencing sperm development and function. In this study, we report on the characterization of BmTSSK3, a TSSK from the silkworm, Bombyx mori. We found that BmTSSK3 is specifically expressed in the testis and localized to the sperm flagella, particularly in the sperm tail cyst. Furthermore, we developed BmTSSK3 inhibitors through molecular docking and binding assays. Small molecules 5-(4-Fluorophenyl)-2-ureidothiophene-3-carboxamide (TPCA-1)and Imidurea were identified to bind to BmTSSK3. Using site-specific mutation technology, we identified amino acid residues R134 and S184 as crucial binding sites for small molecules. RNA interference assay and Western blot analysis showed that knockdown of BmTSSK3 significantly decreased histone 3 phosphorylation. To confirm the inhibitory effect of these small molecules, we treated silkworm testes with TPCA-1 and observed a strong inhibitory effect. TPCA-1 is an inhibitor of BmTSSK3, which raises its potential as a future candidate for male sterility of the silkworm. Thus, this study may offer a novel strategy for sterile silkworms as well as insects. © 2024 Society of Chemical Industry.

Inhibitory effects of toxic Dolichospermum flos-aquae and anatoxin-a on inducible defenses of Daphnia magna

Cyanobacterial blooms, resulting from serious eutrophication, can produce various cyanotoxins and severely disrupt aquatic ecosystems. Inducible defenses are adaptive traits developed by prey in response to predation risks. However, the effects of the increasing proportion of cyanobacteria and cyanotoxins produced during cyanobacterial blooms on the inducible defenses of cladocerans, particularly in terms of behavioral defenses, remain unclear. In this study, we selected Daphnia magna and investigated the defensive traits against predation risks by the predator Rhodeus ocellatus under different ratios of cyanobacteria (Dolichospermum flos-aquae) and green algae (Scenedesmus obliquus), as well as varying concentrations of anatoxin-a (ATX), a cyanotoxin. We recorded the inducible defensive traits involving to morphology, behavior, and offspring production of D. magna. Results showed that the body length of D. magna at sexual maturity and the number of offspring in the first brood were significantly reduced by the presence of D. flos-aquae. Moreover, when the proportion of D. flos-aquae reached 75% and 100%, D. magna did not develop to sexual maturity. Furthermore, D. flos-aquae inhibited the formation of inducible behavioral defense of D. magna, with a stronger inhibitory effect as the proportion of D. flos-aquae increased. In this experiment, the effects of ATX on the morphological traits at sexual maturity and offspring production of D. magna were minor, but ATX still had the potential to inhibit the formation of inducible behavioral defense. We confirmed that changes in the proportion of cyanobacteria and green algae as well as the production of ATX by cyanobacteria during cyanobacterial blooms can affect the growth, development, and inducible defensive traits of cladocerans, potentially altering their population dynamics during such events.

Computational and experimental characterisation of a new (R)-camphor-Thiazolidinone derivative: A combined approach for structure optimisation and activity prediction

This study describes the synthesis, characterisation, in-silico exploration, and theoretical investigation of a novel 5-Methyl-2-(((1S,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)hydrazono)thiazolidin-4-one 3. The structure of the synthesised derivative was successfully confirmed using high-resolution mass spectrometry (HRMS) and 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. In addition, a concise theoretical study was employed to elucidate the experimentally observed stability of the compound. On the computational level, this investigation utilised DFT, molecular docking, and molecular dynamics simulations for the (R)-camphor-thiazolidinone derivative. The optimised structure of compound 3 was predicted with the DFT/B3LYP method with the 6–311++G(d,p) basis set. The theoretical vibrational modes were assigned and found to be consistent with the observed FT-IR spectrum. The simulated NMR values exhibited good agreement with the experimental NMR chemical shifts, with the deviations of 0.5113 and 3.816 ppm for the 1H and 13C, respectively. The UV–vis spectra indicated the n → π* and π → π* transitions in compound 3, with confirmation of intermolecular charge transfer (ICT) from the FMOs and NBO analyses. The MEP surface, Mulliken, and NPA analyses confirm the presence of reactive sites within compound 3. NCI-RDG studies revealed the presence of van der Waals (vdW) interactions and the absence of hydrogen bonding within the studied molecule. The molecular docking analysis indicates that compound 3 exhibits a strong inhibitory effect on the targeted protein 6HQO, which, in turn, is associated with breast cancer. The molecular dynamics analysis validates the accuracy of the docking results.

Identification, Pathogenicity, and Fungicide Sensitivity of Colletotrichum Species Associated with Anthracnose on Italian Ryegrass in Southwestern China.

Italian ryegrass (Lolium multiflorum L.) is widely cultivated as an important forage worldwide because of its high nutritional value and good palatability. Anthracnose caused by Colletotrichum species was a common and new emerging disease of Italian ryegrass. In this study, 88 Colletotrichum isolates were collected from diseased leaves of Italian ryegrass planting regions in Sichuan, Chongqing and Guizhou provinces of southwestern China between 2019 and 2022. By pure culture technique, 15 representative single-spore isolates were obtained for further study. Multi-locus phylogenetic analysis coupled with morphological features showed that these isolates were finally identified as six new record species: C. cereale of the C. graminicola species complex, C. fioriniae and C. nymphaeae of the C. acutatum species complex, C. boninense and C. citricola of the C. boninense species complex, and C. nageiae. Pathogenicity tests indicated that all species could induce anthracnose symptoms; of these, C. cereale was more invasive than other species, followed by C. fioriniae, C. nageiae, C. citricola and C. boninense; C. nymphaeae was weakest pathogenic to Italian ryegrass plants (P ≤ 0.05). Fungicide sensitivity assays showed that iprodione, propineb and oxime·tebuconazole had strong inhibitory effect on the mycelial growth of six Colletotrichum species; in addition, azoxystrobin and fludioxonil also significantly inhibited the mycelial growth of C. nymphaeae and C. fioriniae, respectively. These results provide the basis for the diagnosis and detection in the field, pathogen identification and management of anthracnose on Italian ryegrass.

Reparative effects of Schizophyllum commune oat bran fermentation broth on UVB-induced skin inflammation via the JAK/STAT pathway

Human immortal keratinocyte cells (HaCaT) are induced with UVB to establish an injury model. This model is utilized to investigate whether oat bran fermentation broth (OBF) has a reparative effect on skin inflammation and damage to the skin barrier caused by UVB irradiation. The results show that compared with unfermented oat bran (OB), OBF exhibits higher structural homogeneity, increased molecular weight size, active substances content, and in vitro antioxidant activity. OBF has a scavenging effect on excess reactive oxygen species (ROS) and increases the intracellular levels of antioxidant enzymes. It was found that OBF has a stronger inhibitory effect on the release of inflammatory factors than OB. It increases the synthesis of AQP3 and FLG proteins while decreasing the secretion of KLK-7. OBF can inhibit the transcription level of inflammatory factors by suppressing the JAK/STAT signaling pathway. Safety experiments demonstrate that OBF has a high safety profile.Graphical

Antifungal Activity of Difenoconazole-Loaded Microcapsules against Curvularia lunata.

Difenoconazole-loaded (CS-DIF) microcapsules were synthesized by encapsulating difenoconazole into biocompatible chitosan. The physical and chemical properties indicated that the encapsulation and chemical loading rates were 85.58% and 61.98%, respectively. The microcapsules exhibited prominent controlled-release and surface stability performance. The cumulative release rate was only 33.6% in 168 h, and the contact angle decreased by 11.73° at 120 s compared with difenoconazole. The antifungal activity of the CS-DIF microcapsules against Curvularia lunata was confirmed through observations of colony growth, in vitro and in vivo inoculation, mycelium morphology, as well as DNA and protein leakage. The antioxidant enzyme activity of superoxide dismutase, peroxidase, and catalase decreased by 65.1%, 84.9%, and 69.7%, respectively, when Curvularia lunata was treated with 200 μg/mL microcapsules, compared with the control in 24 h. The enzymatic activity of polyphenol oxidase decreased by 323.8%. The reactive oxygen species contents of hydrogen peroxide and superoxide anions increased by 204.6% and 164%, respectively. Additionally, the soluble sugar and soluble protein contents decreased by 65.5% and 69.6%, respectively. These findings provided a novel approach to control the growth of C. lunata efficiently, laying a foundation for reducing the quantity and enhancing the efficiency of chemical pesticides. The CS-DIF microcapsules exhibited a strong inhibitory effect on fungus, effectively preventing and controlling leaf spot disease and showing potential for field applications. This study might be of great significance in ensuring plant protection strategies.

Interactions of bosutinib with drug transporters: In vitro and In vivo inhibition of organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein by bosutinib

Bosutinib has been approved for use in patients with chronic myeloid leukemia. Information regarding the effects of bosutinib on clinically important drug transporters is limited, particularly regarding its inhibitory potency on transporters and in vivo effects. Therefore, we conducted a study investigating the in vitro and in vivo effects of bosutinib on drug transporters. Bosutinib showed moderate or strong inhibitory effects on organic cation transporter 2, multidrug and toxin extrusion protein 1, and breast cancer resistance protein with IC50 values of 0.0894, 0.598, and 10.8 µM, respectively. In vivo experiments in rats showed that bosutinib significantly inhibited organic cation transporter 2 and multidrug and toxin extrusion protein 1, leading to a marked reduction in the renal clearance of metformin and an increase in systemic exposure to metformin. Bosutinib increased systemic exposure to sulfasalazine, a probe substrate of breast cancer resistance protein, by 75 % in rats, highlighting its potential to significantly affect intestinal drug efflux. These quantitative changes suggest that bosutinib may alter the in vivo pharmacokinetics of drugs that are substrates of these transporters, potentially leading to increased drug exposure and enhanced or unexpected pharmacological effects.

Chiral thioureas containing naphthalene moiety as selective butyrylcholinesterase inhibitors: Design, synthesis, cholinesterase inhibition activity and molecular docking studies

Butyrylcholinesterase (BChE), which plays a role in the regulation of acetylcholine (ACh) as well as cholinergic type neurotransmission, also has non-cholinergic functions such as differentiation, proliferation and apoptosis. The strategy of increasing ACh levels without the typical undesirable effects of AChE inhibitors used in treatment with selective inhibition of BChE may be an effective approach to delay the progression of Alzheimer's disease (AD). Based on this approach, twenty derivatives of chiral thioureas containing the naphthalene moiety (1a-10a and 1b-10b) in both enantiomeric forms were designed, synthesized with good yields (up to 90 %), in this study. Also, their AChE and BChE inhibition activities and antioxidant profiles were tested. All chiral thioureas except compound 5b showed excellent inhibitory activity against BChE but lower inhibitory activity against AChE compared to galantamine. The activity results on BChE revealed that compound 1b (S-enantiomer) had the strongest inhibitory effect on BChE (IC50 = 10.18 ± 1.02 μM) with a selectivity index of 7.27 among all compounds. In terms of antioxidant activity, compound 7a (R-isomer) exhibited the overall highest antioxidant profile in the series of chiral thioureas. Molecular docking studies were used to reveal the interactions of the most active compounds with target enzymes. Besides, an estimation of the drug-likeness and pharmacokinetic properties of all chiral thioureas was performed.

A new thermodynamic model for predicting the 3-D phase equilibrium surface of gas hydrates considering the effect of salt concentration

An accurate understanding of the thermodynamic stability of gas hydrates in salt-bearing systems is of great significance for predicting the extent of hydrate accumulation and determining the hydrate decomposition domain. Therefore, this study proposes a thermodynamic model for predicting the temperature–pressure-salt concentration three-dimensional phase-equilibrium surface. The model considered the interaction of the electrolyte in a mixed salt solution system and non-spherical shaped hydrate crystal cavity. The modified van der Waals-Platteeuw (vdW-P) model and Benedict-Webb-Rubin-Starling (BWRS) equation of state were used to describe the hydrate phase. The Pitzer-Debye-Hückel equation and nonelectrolyte non random two liquid non random factor (N-NRTL-NRF) activity coefficient model were used to describe the fluid phase. The prediction results of the model agreed with the experimental data, and the absolute average relative deviation in temperature (AARD-T) under pure water conditions was only 0.08, and the AARD-T under electrolyte conditions did not exceed 0.15, which proved the accuracy and reliability of the model. The calculation results showed that when the mole fraction of chloride salt was greater than 0.02 and the pressure was higher than 20 MPa, chemical factors caused the p-T curves to translate. When the pressure was low, the temperature gradient along the direction of the salt concentration changed drastically, and the p-T curves no longer had translation characteristics. In comparison, under the same mole fraction, AlCl3 had a stronger inhibitory effect on the CH4 hydrate than the other chloride salts. The lnp-X-1/T three-dimensional surface of the CH4 hydrate exhibited good Clausius-Clapeyron linear behavior locally, and the surface had certain nonlinear characteristics. The degree of nonlinearity of the lnp-X-1/T three-dimensional surfaces of different types of chloride salts was different. A better inhibitory effect of the chloride salt electrolyte on the CH4 hydrate was associated with stronger nonlinearity between 1/T and lnp.

Two symmetric Schiff base complexes: Inhibition of cell proliferation, inducing apoptosis and suppressing migration

Two complexes [Cu4L4] (1) and [Zn2Cl4L]·2[N(CH2CH3)4] (2) are synthesized and characterized with UV–Vis, IR, PXRD and TGA using a symmetrical flexible Schiff base ligand 2,2′-(1,4-phenlenebis(nitrilomethylylidene)-bis(6- methoxyphenol) (H2L). Crystallographic analysis reveals that complex 1 is a mirror symmetric single molecule with a rhombic crossing structure linked by four Cu(II) ions and four ligands encircling each other. Complex 2 is a centrosymmetric single molecule with one ligand connecting two zinc chloride salts to form an anion framework with two tetraethylammonium cations to balance charge. Antiproliferative activity of both complexes against four cancer cells and two normal cells was investigated, and the results show that complex 2 had the strongest inhibitory effect on A549 cells with IC50 value much lower than cisplatin and lower toxicity to two normal cells. Mechanistic studies showed that complex 2 could induce apoptosis of A549 cells, and inhibit cell invasion and migration of SMMC-7721 cells and A549 cells at a low concentration effectively. This work could provide a basis for developing novel metal-based anticancer agents.

Design, synthesis, and antitumor activity evaluation of BF3-o, m, p-phenylenediamine bridged with pyrimidine-indole BF3 adduction derivatives.

Fluorescent drugs and pyrimidine-indole scaffolds have been shown to have advantages in cancer treatment. Fluorescent antitumor drugs BF3-o, m, p-phenylenediamine pyrimidine-indole derivatives (PYB1, PYB2, and PYB3) were synthesized by linking pyrimidine and indole groups with aniline through a simple step and introducing BF3. The drugs exhibit promising antitumor activity and their fluorescent properties make them useful for imaging purposes. The optical properties of the three compounds have been investigated. All of them have fluorescent properties and compound PYB2 has good fluorescent properties. Additionally, the in vitro cytotoxicity of these compounds was evaluated against the human cancer cell line HeLa and the human normal cell line L02. The inhibition rates of HeLa cells treated with PYB1, PYB2, and PYB3 at a concentration of 19.2μg/mL were 80.91%, 77.72%, and 65.94%, respectively. These results indicate a strong inhibitory effect on cancer cells. Further through the cell imaging experiment, we can see that PYB2 can enter the cell through the cell membrane through the fluorescence scattering diagram, which has good biocompatibility. In addition, the possible interactions between the compounds and Ras protein active sites were analyzed by molecular docking. The three compounds can bind well to Ras protein through hydrogen bonding. This study provides a basis for the development and modification of pyrimidine-indole fluorescent anticancer drugs. Compound PYB2 shows potential as a fluorescent anticancer drug.

Amino acid mutation of succinate dehydrogenase complex induced resistance to benzovindiflupyr in Magnaporthe oryzae

Magnaporthe oryzae is a rice blast pathogen that seriously threatens rice yield. Benzovindiflupyr is a succinate dehydrogenase inhibitor (SDHI) fungicide that effectively controls many crop diseases. Benzovindiflupyr has a strong inhibitory effect on M. oryzae; however, control of rice blast by benzovindiflupyr and risk of resistance to benzovindiflupyr are not well studied in this pathogen. In this study, six benzovindiflupyr-resistant strains were obtained by domestication induced in the laboratory. The MoSdhBH245D mutation was the cause of M. oryzae resistance to benzovindiflupyr, which was verified through succinate dehydrogenase (SDH) activity assays, molecular docking, and site-specific mutations. Survival fitness analysis showed no significant difference between the benzovindiflupyr-resistant and parent strains. Positive cross-resistance to benzovindiflupyr and other SDHIs and negative cross-resistance to azoxystrobin were observed. Therefore, the risk of benzovindiflupyr resistance in M. oryzae might be medium to high. It should be combined with other classes of fungicides (tebuconazole and azoxystrobin) to slow the development of resistance.

Whey protein isolate‐oligosaccharides conjugates as encapsulants improving stability of L. lactis

SummaryThe aim of this study is to prepare Maillard reaction products (MRPs) with low Browning intensity for microencapsulation of Lactococcus lactis and to improve its processing stability and anti‐digestive ability. In this study, whey protein isolate (WPI) was combined with xylose oligosaccharides (XOS) and feruloyl oligosaccharides (FOs) at 90 °C for 90 min to prepare two Maillard reaction products (MRPs), which were applied to the construction of L. lactis microcapsules. The results showed that WPI‐FOs had a lower Browning intensity and slightly lower intermediate content than WPI‐XOS. Both MRPs showed strong inhibitory effects on the pathogens and probiotics effect on L. lactis. In addition, L. lactis coated with MRPs showed significantly enhanced resistance to heat and mechanical stress. Therefore, this study demonstrated that the Maillard conjugation of WPI with oligosaccharides has the potential to be the encapsulant for probiotic microcapsules.

Sugar derived hydrochar catalysts for enhanced biodiesel production via esterification

Sugars and sugar alcohols are renewable raw materials which can be used for char production. Their acid-catalyzed hydro-carbonization results in the formation of carbon materials with acidic functional groups on the surface, which makes them suitable to be used as heterogeneous catalysts in esterification reactions. Hydrochars materials were prepared by low-temperature slow carbonization of glycerol, xylitol, sucrose, and glucose in the presence of different amounts of H2SO4 (mass ratios from 1 to 4). The hydrochars were extensively characterized and tested in the methanolysis reaction of oleic acid. All the carbon materials were amorphous with features of polyaromatic sheets with hydroxyl (–OH), carboxylic acid (–COOH), and sulfonic (−SO3H) functional groups. The effect of the oleic acid water content on catalytic performance was studied, showing a strong inhibition effect due to the hygroscopic character of catalysts induced by sulfonic groups and other surface groups with oxygen. Under the conditions evaluated (5 % wt. of catalyst, methanol/oleic acid = 9 M ratio, methanol reflux temperature) the sucrose-derived catalyst prepared with the highest H2SO4 content showed the best performance, leading to methyl oleate yield > 90 % after 2 h of reaction, which is only achieved by the majority of analogous catalysts reported in the literature after 4 to 8 h of reaction. The data showed that there is a correlation between the methyl ester yield and the graphitization of the catalyst, as this makes the catalyst more hydrophobic, which is an advantage in esterification catalysts.

Butyrate induces higher host transcriptional changes to inhibit porcine epidemic diarrhea virus strain CV777 infection in porcine intestine epithelial cells

Newborn piglets’ health is seriously threatened by the porcine epidemic diarrhea virus (PEDV), which also has a significant effect on the pig industry. The gut microbiota produces butyrate, an abundant metabolite that modulates intestinal function through many methods to improve immunological and intestinal barrier function. The objective of this investigation was to ascertain how elevated butyrate concentrations impacted the host transcriptional profile of PEDV CV777 strain infection. Our findings showed that higher concentrations of butyrate have a stronger inhibitory effect on PEDV CV777 strain infection. According to RNA-seq data, higher concentrations of butyrate induced more significant transcriptional changes in IPEC-J2 cells, and signaling pathways such as PI3K-AKT may play a role in the inhibition of PEDV CV777 strain by high concentrations of butyrate. Ultimately, we offer a theoretical and experimental framework for future research and development of novel approaches to harness butyrate’s antiviral infection properties.

THE CHALLENGES OF MEDICAL RESOURCE LIMITATIONS FOR TUBERCULOSIS UNDER THE COVID-19 PANDEMIC: A MATHEMATICAL MODELING OF CO-INFECTION AND OPTIMAL CONTROL

Currently, more than 600 million people worldwide are diagnosed with COVID-19, while the implication of Tuberculosis cannot be ignored. The combination of COVID-19 and Tuberculosis exacerbates the catastrophe, dealing a serious blow to the healthcare system. This paper addresses how to develop effective and reasonable programs to combat the spread of COVID-19 and Tuberculosis in the absence of Tuberculosis medical resources, as well as exploring the impact of medical resources on optimal control implementation. Therefore, a co-infection dynamic of COVID-19 and Tuberculosis is constructed and analyzed. In order to investigate approaches to mitigate the disease transmission, a comprehensive and integrated study including sensitivity analysis, optimal control design and cost-effectiveness analysis is then performed. The simulation results illustrate that, the combination of the three control measures effectively achieves a win-win result in economic and epidemiological terms. In addition, the impact of Tuberculosis medical resources is highlighted, and the study shows that an appropriate increase in the medical resource supply for Tuberculosis during optimal control can have a stronger inhibitory effect on co-infection. Finally, based on the actual data, the model is validated by fitting the cumulative confirmed case curves of the two diseases.

Genome Sequence Resource of Bacillus mojavensis KRS009, a Rhizospheric Microorganism with Biocontrol Potential

Bacillus mojavensis KRS009 was identified as an antagonistic strain with a strong inhibitory effect on various phytopathogenic fungi. To provide further insight into its biocontrol mechanisms and ability to improve plant salt tolerance, the high quality complete genome of KRS009 was sequenced by PacBio platform and assembled using PacBio-HiFiReads. The KRS009 genome consists of one circular chromosome of 4,089,687 bp with 43.5% GC content and 4,062 open reading frames, of which 3,920 protein-coding genes, 86 transfer RNA, 10 ribosomal RNA, and 26 small RNA were identified in this genome. Among them, genes related to compatible solutes, including treC, galU, proX, and proW, are involved in the synthesis of trehalose, proline, and betaine metabolism and play an important role in relieving osmotic stress. In addition, the KRS009 genome contains genes associated with high salinity tolerance, including those responsible for Na+/H+ antiporters, K+ transporters, TrkH thiamin phosphate synthase, K+-sensing histidine kinase, aryl-phospho-beta-D-glucosidase, flavoprotein CzcO associated with the cation diffusion facilitator CzcD, and chaperonin GroEL. Together, the high-quality genome resource of strain KRS009 would provide a molecular basis for further research on its biocontrol and plant salt tolerance mechanisms. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Antimycobacterial and Anticancer Properties of Myrtus communis Leaf Extract.

Plant-derived products or extracts are widely used in folk/traditional medicine to treat several infections, ailments, or disorders. A well-known medicinal herb, Myrtus communis is an evergreen fragrant plant native to the Mediterranean region that has been used for ages in traditional medicine around the world. The microplate alamarBlue assay and the well diffusion method were used to evaluate the zone of inhibition and MIC, respectively. The double-disc diffusion method was used to investigate the synergy between antibiotics and the extract. The crystal violet method was used to investigate biofilm development. The SulphoRhodamine-B assay and DNA flow cytometry were used to investigate the proliferation and subsequent distribution of cells among different phases of the cell cycle. The apoptotic and necrotic phases of the cancer cells were examined using flow cytometry in conjunction with Annexin V-FITC/PI labeling. Using the IBM SPSS statistical program, a one-way ANOVA with Tukey's post hoc test was employed for statistical analysis. The ethanolic leaf extract of M. communis showed a strong growth inhibition effect (zone of inhibition: 20.3 ± 1.1-26.3 ± 2.5 mm, MIC: 4.88-312.5 µg/mL, and MBC: 39.07-1250 μg/mL) against several rapidly growing and slow-growing mycobacterial strains in a dose-dependent manner. Damage to the cell wall of bacterial cells was determined to be the cause of the antimycobacterial action. The extract inhibited biofilm formation (MBIC of 9.7 µg/mL) and eradicated already-formed mature and ultra-mature biofilms of M. smegmatis, with MBEC values of 78 µg/mL and 156 µg/mL, respectively. Additionally, the extract exhibited potent anticancer effects against diverse cancer cell lines of the breast (MCF-7), liver (HepG2), cervix (HeLa), and colon (HCT116) (IC50 for HCT116: 83 ± 2.5, HepG2: 53.3 ± 0.6, MCF-7: 41.5 ± 0.6, and HeLa: 33.3 ± 3.6) by apoptosis after arresting the cells in the G1 phase of the cell cycle. These results suggest that M. communis leaf extract is a potential source of secondary metabolites that could be further developed as potential anticancer and antimycobacterial agents to treat diverse types of cancers and mycobacterial infections.

Investigating the Underlying Molecular Mechanisms of Yunke on Bone Metastases from Prostate Cancer.

To explore analgesic effect and bone repair mechanism of non-radioactive technetium-99 conjugated with methylene diphosphonate (99Tc-MDP, brand name, Yunke) on bone metastases (BM). In vivo experiment, mouse BM models of prostate cancer RM-1 cell were constructed and divided into Control, Yunke, 99Tc+SnCl2 and MDP groups based on medicine composition. Tumor specimens were inspected for size, X-ray, microCT and histopathology. In vitro experiment, with Cell Counting Kit-8 (CCK8), scratch, clone, apoptosis, Polymerase Chain Reaction (PCR) and Western Blot experiments, effects of Yunke on RM-1 cells and osteoclast-related cells were observed. In vivo experiment, there was no difference in tumor size between Yunke and control group. Contrasted with control group, in Yunke group, trabecular spacing (Tb.Sp) of tumor bone was lower, bone volume/total volume (BV/TV) on marrow cavity and bone cortex were higher. Tunnel staining showed that positive rate of apoptosis in Yunke group was higher than that in control group. Ki67 staining showed that Yunke could not inhibit proliferation of tumor cells. In vitro experiment, CCK8 and scratch experiments showed that Yunke neither can inhibit proliferation nor can inhibit migration of RM-1 cells. High concentration of Yunke promoted late apoptosis of RM-1 cells. Yunke could inhibit BMM cell proliferation, differentiation of osteoclasts, and osteoclast-related transcription factors. Yunke displayed different degrees of inhibitory effects on MAPKs signaling pathway during osteoclast differentiation. It had obvious inhibitory effects on osteoclast-related transcription factors, such as cFOS, NFATC1, ACP-5, CTSK, D2 and MMP-9, the strongest inhibitory effects were observed with ACP-5, CTSK and D2. Yunke also displayed different degrees of inhibitory effects on protein activities of JNK, pERK, ERK and pP38. Yunke cannot inhibit the proliferation and migration of RM-1 cells, so we think it is not recommended for the treatment of primary tumors and prevention of occurrence of tumors metastatic to bones. The mechanism of therapeutic effect of Yunke on BM by inhibiting proliferation of BMM, inhibiting MAPKs signal transduction and activation of transcription factors during differentiation process of BMM-derived osteoclasts, inhibiting number and size of osteoclasts, inhibiting bone resorption and protecting bone destruction through enhancing bone hardness and bone mass. Thereby, we believe that Yunke is more suitable for promoting the repair induced by BMs, delaying its progression and reducing the occurrence of SREs.

Insight into the Manipulation Mechanism of Polymorphic Transformation by Polymers: A Case of Cimetidine.

Employing polymer additives is an effective strategy to realize the manipulation of polymorphic transformation. However, the manipulation mechanism is still not clear, which limit the precise selection of polymeric excipients and the development of pharmaceutical formulations. The solubility of cimetidine (CIM) in acetonitrile/water mixtures were measured. And the polymorphic transformation from CIM form A to form B with the addition of different polymers was monitored by Raman spectroscopy. Furthermore, the manipulation effect of polymers was determined based on the results of experiments and molecular simulations. The solubility of form A is consistently higher than that of form B, which indicate that form B is the thermodynamically stable form within the examined temperature range. The presence of polyvinylpyrrolidone (PVP) of a shorter chain length could have a stronger inhibitory effect on the phase transformation process of metastable form, whereas polyethylene glycol (PEG) had almost no impact. The nucleation kinetics experiments and molecular dynamic simulation results showed that only PVP molecules could significantly decrease the nucleation rate of CIM, due to the ability of reducing solute molecular diffusion and solute-solute molecular interaction. A combination of crystal growth rate measurements and calculations of the interaction energies between PVP and the crystal faces of CIM indicate that smaller molecular weight PVP can suppress crystal growth more effectively. PVP K16-18 has more impact on the stabilization of CIM form A and inhibition of the phase transformation process. The manipulation mechanism of polymer additives in the polymorphic transformation of CIM was proposed.