Efficacy of an herbal formula Guixiong Yimu San in preventing retained placenta and improving reproductive performance in cows.

Retained placenta is a common health issue, and appropriate prevention strategies are effective in postpartum health management. This study aimed to evaluate whether early intervention using GYS can prevent retained placenta and puerperal metritis, as well as enhance reproductive outcomes in cows. Each bovine in the GYS group (n = 591) received a single prophylactic dose of GYS (0.5 g/kg body weight) orally within 2 h after parturition, while those in the control group (n = 598) received no intervention. GYS treatment was associated with a decreased incidence of retained placenta (4.6% vs. 12.0%, P < 0.01, OR = 0.335), a lower puerperal metritis risk (8.8% vs. 20.1%, P < 0.01, OR = 0.369), and a reduced need for additional therapeutic antibiotics (11.2% vs. 26.1%, P < 0.01, OR = 0.342). We observed increases in the first service conception rate (59.7% vs. 49.1%, P < 0.01) and conception rate within 305 days postpartum (93.2% vs. 85.5%, P < 0.01) in the GYS group than in the control group. A significant decrease was observed in the number of services per conception (1.8 ± 1.1 vs. 2.1 ± 1.4, P < 0.01) and the calving-to-conception interval (83.6 ± 39.6 vs. 96.6 ± 52.5 days, P < 0.01) between the two groups. Additionally, GYS treatment increased milk yield on days 7, 14, and 28 postpartum without affecting milk fat, milk protein, somatic cell count (SCC), or milk urea nitrogen (MUN) on days 7 and 28 postpartum. Accordingly, the GYS was effective and safe in preventing retained placenta and to improve reproductive performance in cows. Therefore, it could be a prophylactic intervention for superior postpartum fertility in cows.

Enhanced Tunability of Dual-Band Chiral Metasurface in the Mid-Infrared Range via Slotted Nanocircuit Design.

Multi-band circular dichroism (CD) response and tunability on the chiral metasurface are crucial for this device's applications in sensing and detection. This work proposes a dual-band CD Au-CaF2-Au dimer elliptical metasurface absorber, where chiroptical sensing is realized by breaking the geometric symmetry between two ellipses. The proposed metasurface can achieve high CD values of 0.8 and -0.74 for the dual-band within the 3-5 µm region, and the CD values can be manipulated by independently adjusting the geometric parameters of the metasurface. Furthermore, a slotted nanocircuit is introduced onto the metasurface to enhance its tunability by manipulating the geometry parameter in the design process, and the related mechanism is explained using an equivalent circuit model. The simulation of the sensing model revealed that the slotted nanocircuit enhances the sensor's tunability and significantly improves its bandwidth and sensitivity, achieving peak enhancements at approximately 753 nm and 1311 nm/RIU, respectively. Due to the strong dual-band positive (and negative) responses of the CD values, flexible wavelength tunability, and nonlinear sensitivity enhancement, this design provides a new approach for the development and application of mid-infrared chiroptical devices.

Battling Salmonella enteritidis infections: integrating proteomics and in vivo assessment of Galla Chinensis tannic acid.

Salmonella infections pose a significant threat to animal and human health. Phytochemicals present a potential alternative treatment. Galla chinensis tannic acid (GCTA), a hydrolyzable polyphenolic compound, inhibits bacterial growth and demonstrates potential as an alternative or supplement to antibiotics to prevent Salmonella infections. However, little is known about the antimicrobial mechanism of GCTA against Salmonella. Here, we revealed 456 differentially expressed proteins upon GCTA treatment, impacting pathways related to DNA replication, repair, genomic stability, cell wall biogenesis, and lipid metabolism using TMT-labeled proteomic analysis. TEM analysis suggested altered bacterial morphology and structure post-treatment. A Salmonella-infected-mouse model indicated that GCTA administration improved inflammatory markers, alleviated intestinal histopathological alterations, and reduced Salmonella enterica serovar Enteritidis (S. Enteritidis) colonization in the liver and spleen of Salmonella-infected mice. The LD50 of GCTA was 4100 mg/kg with an oral single dose, vastly exceeding the therapeutic dose. Thus, GCTA exhibited antibacterial and anti-infective activity against S. Enteritidis. Our results provided insight into the molecular mechanisms of these antibacterial effects, and highlights the potential of GCTA as an alternative to antibiotics.

Novel Drug Delivery Systems: An Important Direction for Drug Innovation Research and Development.

The escalating demand for enhanced therapeutic efficacy and reduced adverse effects in the pharmaceutical domain has catalyzed a new frontier of innovation and research in the field of pharmacy: novel drug delivery systems. These systems are designed to address the limitations of conventional drug administration, such as abbreviated half-life, inadequate targeting, low solubility, and bioavailability. As the disciplines of pharmacy, materials science, and biomedicine continue to advance and converge, the development of efficient and safe drug delivery systems, including biopharmaceutical formulations, has garnered significant attention both domestically and internationally. This article presents an overview of the latest advancements in drug delivery systems, categorized into four primary areas: carrier-based and coupling-based targeted drug delivery systems, intelligent drug delivery systems, and drug delivery devices, based on their main objectives and methodologies. Additionally, it critically analyzes the technological bottlenecks, current research challenges, and future trends in the application of novel drug delivery systems.

Regulation and analysis of Simiao Yong'an Decoction fermentation by Bacillus subtilis on the diversity of intestinal microbiota in Sprague-Dawley rats.

Background and Aim: Simiao Yong'an decoction (SYD) is a classic traditional Chinese medicine (TCM) prescription that has the effects of clearing heat, detoxifying, promoting blood circulation, and relieving pain. In this study, we investigated the effect of SYD on the diversity of intestinal microbiota after fermentation by Bacillus subtilis. Materials and Methods: SYD was fermented using B. subtilis. Female Sprague-Dawley rats were randomly divided into the following four groups with six rats in each group: Negative sample group (NS), water exaction non-fermentation group (WE), B. subtilis group (BS), and fermentation liquid group (FL). All rats were orally administered for 14 days. High-throughput Illumina sequencing was used to analyze 16S rRNA expression in rat fecal samples. Results: A total of 2782 operational taxonomical units (OTUs) were identified in this study, and 634 OTUs were shared among all samples. Bacteroidetes (28.17%-53.20%) and Firmicutes (48.35%-67.83%) were the most abundant phyla identified among the four groups. The abundance of Escherichia and Alistipes was lower in the FL group than in the NS group, whereas the abundance of Bifidobacteria and Lactobacillus was increased in the FL group (p < 0.05). The abundance of Bifidobacterium was significantly upregulated in the FL group compared with the WE and BS groups (p < 0.05). Conclusion: After fermentation, SYD had a significantly better effect than SYD or B. subtilis. SYD significantly promoted the growth of intestinal probiotics, inhibited the growth of pathogenic bacteria, and maintained the balance of intestinal microbiota in SD rats. This study provides new insights into the development and use of SYD.

Advances in Flavonoid Research: Sources, Biological Activities, and Developmental Prospectives.

At present, the occurrence of a large number of infectious and non-communicable diseases poses a serious threat to human health as well as to drug development for the treatment of these diseases. One of the most significant challenges is finding new drug candidates that are therapeutically effective and have few or no side effects. In this respect, the active compounds in medicinal plants, especially flavonoids, are potentially useful compounds with a wide range of pharmacological activities. They are naturally present in nature and valuable in the treatment of many infectious and non-communicable diseases. Flavonoids are divided into fourteen categories and are mainly derived from plant extraction, chemical synthesis and structural modification, and biosynthesis. The structural modification of flavonoids is an important way to discover new drugs, but biosynthesis is currently considered the most promising research direction with the potential to revolutionize the new production pipeline in the synthesis of flavonoids. However, relevant problems such as metabolic pathway analyses and cell synthesis protocols for flavonoids need to be addressed on an urgent basis. In the present review, new research techniques for assessing the biological activities of flavonoids and the mechanisms of their biological activities are elucidated and their modes of interaction with other drugs are described. Moreover, novel drug delivery systems, such as nanoparticles, bioparticles, colloidals, etc., are gradually becoming new means of addressing the issues of poor hydrophilicity, lipophilicity, poor chemical stability, and low bioavailability of flavonoids. The present review summarizes the latest research progress on flavonoids, existing problems with their therapeutic efficacy, and how these issues can be solved with the research on flavonoids.

Transcriptomic analysis and knockout experiments reveal the role of suhB in the biocontrol effects of Pantoea jilinensis D25 on Botrytis cinerea.

Tomato gray mold, caused by Botrytis cinerea, is an important disease in tomato. Pantoea jilinensis D25, isolated form tomato rhizosphere soil, can prevent B. cinerea infection in tomato. To determine the underlying biocontrol mechanism, the transcriptome of P. jilinensis D25 was assessed. Differential expression analysis revealed that 941 genes were upregulated and 997 genes were downregulated. Through transcriptome analysis, the suhB gene was knocked out. ΔPj-suhB exhibited lower swimming motility and colonization abilities than strain D25. After 4 days of co-cultivation, ΔPj-suhB could reduce the colony diameter, mycelial weight, and spore production of B. cinerea with the inhibitory rates of 31.72 %, 39.62 %, and 47.42 %, respectively, compared with control. However, the inhibitory rates of strain D25 were 52.91 %, 60.09 %, and 76.85 %, respectively, compared with control. Strain D25 could significantly downregulate pathogenesis-related genes in B. cinerea, whereas the expression level of these genes in B. cinerea was higher after treatment with ΔPj-suhB than after that with strain D25. In vitro experiments revealed that the lesion area and disease control efficacy were 1.520 and 0.038 cm2 and 68.7 % and 99.0 %, respectively, after ΔPj-suhB and strain D25 treatments. Pot experiments revealed that ΔPj-suhB and strain D25 could prevent tomato plants from B. cinerea infection with the disease reduction rate of 37.5 % and 75.0 %, respectively. Though the activities of defense-related enzymes and expression level of defense related genes in tomato plants were increased under ΔPj-suhB treatment, these effects were higher after strain D25 treatment. Thus, these results demonstrated that suhB was the key gene in strain D25 underlying its biocontrol effect and mobility.

The Morphology and Ultrastructure of Dermal Telocytes Characterized by TEM and AFM.

This investigation delves into the structural foundation of human dermal telocytes (TCs) with the aim of elucidating their role in signal transmission. Dermal TCs were isolated from human foreskins via enzymatic digestion and flow cytometric sorting, and identified by immunohistochemical staining with an antibody against CD34. The ultrastructure of TCs was examined using transmission electron microscopy (TEM). The proliferation rates of sorted TCs and CD34-negative fibroblasts were compared using the MTS assay (Cell Proliferation Assay). Images of viable cultured TCs were analyzed using atomic force microscopy (AFM) under normal atmospheric pressure and temperature. Results demonstrated that dermal TCs were positive for CD34 and vimentin, predominantly distributed in the reticular dermis and subcutaneous tissue, forming interwoven networks. Each TC had a small body with a high nuclear-plasma ratio and two or three extremely long and thin telopodes (TPs), exhibiting a typical 'moniliform' appearance. Compared with CD34-negative fibroblasts, dermal TCs exhibited significantly lower proliferation rates. Cultured TCs displayed typical moniliform projections (namely, TPs) in the AFM images. The distal ends of TPs were enlarged, shaped like a broom, and extended multiple pseudopods to contact other cell bodies. Slender filamentary pseudopodia and thick, short cone-like structures were observed on the surfaces of the dilated segments and terminals of TPs. These structures are assumed to be evidence of the secretion and release of endosomes, such as exosomes, and the communication between cells. TCs form interstitial networks in the reticular dermis and subcutaneous tissue, providing a structural basis for contacts between cells and the secretion of signal-carrying substances, involving intercellular connections and communication.

Pantoea jilinensis D25 enhances tomato salt tolerance via altering antioxidant responses and soil microbial community structure.

As a major challenge to global food security, soil salinity is an important abiotic stress factor that seriously affects the crop growth and yield. In this study, the mechanism of salt resistance of Pantoea jilinensis D25 and its improving effect on salt tolerance of tomato were explored with salt resistance-related genes identified in strain D25 by genomic sequencing. The results showed that in comparison with the treatment of NaCl, strain D25 significantly increased the fresh weight, shoot length, root length, and chlorophyll content of tomato under salt stress by 46.7%, 20%, 42.4%, and 44.2%, respectively, with increased absorptions of various macronutrients and micronutrients and decreased accumulation of Na+. The activities of defense enzymes (peroxidase, catalase, superoxide dismutase, phenylalanine ammonia-lyase, and polyphenol oxidase) were enhanced, while the content of malondialdehyde was decreased. The results of quantitative real-time PCR analysis showed that the expressions of genes (SlSOS1, SlNHX1, SlHKT1.1, SlSOD1, SlAPX2, SlAOS, SlPin II, Solyc08g066270.1, Solyc03g083420.2 and SlGA20ox1) related to ion transporters, antioxidant machinery, key defense, serine/threonine protein kinase synthesis, and gibberellin (GA) signal protein were up-regulated and were the highest in the treatment of both NaCl and strain D25. The activities of enzymes (dehydrogenase, urease, invertase, and catalase activities) related to soil fertility were enhanced. The results of 16S rRNA sequencing showed that soil microbial diversity and the abundance of probiotics (e.g., Acidibacter, Limnobacter, and Romboutsia) were significantly increased. Our study provided strong experimental evidence to support the agricultural application of strain D25 in the promotion of growth in crops.

Development of magnetic molecularly imprinted polymers for selective extraction of Benzoxazolinone-type alkaloids from acanthus plants.

Benzoxazolinone-type alkaloids found in Acanthus ebracteatus and Acanthus ilicifolius Linnaeus possess various beneficial properties, such as antileishmanial, antipyretic, analgesic, antibacterial, and antioxidant effects. In this study, we employed a surface imprinting technique on nanomaterials. We utilized functionalized Fe3O4@SiO2NH2 as a scaffold, with 2-benzoxazolinone and 2H-1,4-benzoxazin-3(4H)-one serving as dual templates, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, and 2,2-azodiisobutyric nitrile (AIBN) as the initiator. Prior to polymerization, we screened functional monomers using ultraviolet (UV) spectroscopy. The resulting magnetic surface molecular imprinting polymer (Fe3O4@SiO2@MIP) was thoroughly characterized using Fourier transform infrared spectrometry (FT-IR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We also conducted assessments of its adsorption isotherms, dynamics, and selective binding capabilities. Our findings indicate that the MIPs exhibited exceptional selective recognition performance. Through meticulous screening and optimization of extraction and separation conditions, we established an LC‒MS/MS method based on magnetic solid-phase extraction technology. The method exhibited a recovery range of 78.80-106.99 % (RSD, 0.46-3.31 %) for 2-benzoxazolinone, with a limit of detection (LOD) and limit of quantification (LOQ) of 2.85 and 9.00 µg L-1, respectively. For 2H-1,4-benzoxazin-3(4H)-one, the method yielded a recovery range of 84.75-103.53 % (RSD, 0.07-5.96 %), with an LOD and LOQ of 3.60 and 12.60 µg L-1, respectively, in real samples. The resulting Fe3O4@SiO2@MIP demonstrated a high capacity for class-specific adsorption.

Distributional comparison of different AAV vectors after unilateral cochlear administration.

The adeno-associated virus (AAV) gene therapy has been widely applied to mouse models for deafness. But, AAVs could transduce non-targeted organs after inner ear delivery due to their low cell-type specificity. This study compares transgene expression and biodistribution of AAV1, AAV2, Anc80L65, AAV9, AAV-PHP.B, and AAV-PHP.eB after round window membrane (RWM) injection in neonatal mice. The highest virus concentration was detected in the injected cochlea. AAV2, Anc80L65, AAV9, AAV-PHP.B, and AAV-PHP.eB transduced both inner hair cells (IHCs) and outer hair cells (OHCs) with high efficiency, while AAV1 transduced IHCs with high efficiency but OHCs with low efficiency. All AAV subtypes finitely transduced contralateral inner ear, brain, heart, and liver compared with the injected cochlea. In most brain regions, the enhanced green fluorescent protein (eGFP) expression of AAV1 and AAV2 was lower than that of other four subtypes. We suggested the cochlear aqueduct might be one of routes for vectors instantaneously infiltrating into the brain from the cochlea through a dye tracking test. In summary, our results provide available data for further investigating the biodistribution of vectors through local inner ear injection and afford a reference for selecting AAV serotypes for gene therapy toward deafness.

Study on the Alleviating Effect and Potential Mechanism of Ethanolic Extract of Limonium aureum (L.) Hill. on Lipopolysaccharide-Induced Inflammatory Responses in Macrophages.

Inflammation is the host response of immune cells during infection and traumatic tissue injury. An uncontrolled inflammatory response leads to inflammatory cascade, which in turn triggers a variety of diseases threatening human and animal health. The use of existing inflammatory therapeutic drugs is constrained by their high cost and susceptibility to systemic side effects, and therefore new therapeutic candidates for inflammatory diseases need to be urgently developed. Natural products are characterized by wide sources and rich pharmacological activities, which are valuable resources for the development of new drugs. This study aimed to uncover the alleviating effect and potential mechanism of natural product Limonium aureum (LAH) on LPS-induced inflammatory responses in macrophages. The experimental results showed that the optimized conditions for LAH ultrasound-assisted extraction via response surface methodology were an ethanol concentration of 72%, a material-to-solvent ratio of 1:37 g/mL, an extraction temperature of 73 °C, and an extraction power of 70 W, and the average extraction rate of LAH total flavonoids was 0.3776%. Then, data of 1666 components in LAH ethanol extracts were obtained through quasi-targeted metabolomics analysis. The ELISA showed that LAH significantly inhibited the production of pro-inflammatory cytokines while promoting the secretion of anti-inflammatory cytokines. Finally, combined with the results of network pharmacology analysis and protein expression validation of hub genes, it was speculated that LAH may alleviate LPS-induced inflammatory responses of macrophages through the AKT1/RELA/PTGS2 signaling pathway and the MAPK3/JUN signaling pathway. This study preliminarily revealed the anti-inflammatory activity of LAH and the molecular mechanism of its anti-inflammatory action, and provided a theoretical basis for the development of LAH as a new natural anti-inflammatory drug.

Acute and 28-Day Repeated-Dose Oral Toxicity of the Herbal Formula Guixiong Yimu San in Mice and Sprague-Dawley Rats.

To evaluate the acute and chronic 28-day repeated-dose oral toxicity of Guixiong Yimu San (GYS) in mice and rats, high-performance liquid chromatography (HPLC) was used to determine the stachydrine hydrochloride in GYS as the quality control. In the acute toxicity trial, the mice were administered orally at a dose rate of 30.0 g GYS/kg body weight (BW) three times a day. The general behavior, side effects, and death rate were noticed for 14 days following treatment. In the subacute toxicity trial, the rats were administered orally at a dose rates of30.0, 15.0, and 7.5 g GYS/kg BW once a day for 28 days. The rats were monitored every day for clinical signs and deaths; changes in body weight and relative organ weights (ROW) were recorded every week, hematological, biochemical, and pathological parameters were also examined at the end of treatment. The results showed that the level of stachydrine hydrochloride in GYS was 2.272 mg/g. In the acute toxicity trial, the maximum-tolerated dose of GYS was more than 90.0 g/kg BW, and no adverse effects or mortalities were noticed during the 14 days in the mice. At the given dose, there were no death or toxicity signs all through the 28-day subacute toxicity trial.The oral administration of GYS at a dose rate of 30.0 g/kg/day BW had no substantial effects on BW, ROW, blood hematology, gross pathology, histopathology, and biochemistry (except glucose), so 30.0 g/kg BW/day was determined as the no-observed-adverse-effect dosage.

Antifungal activity of Klebsiella grimontii DR11 against Fusarium oxysporum causing soybean root rot.

AIMS: Soybean root rot, caused by Fusarium oxysporum, leads to significant economic and financial losses to the soybean processing industry globally. In the study, we aimed to explore a biocontrol agent to combat F. oxysporum infection in soybean. METHODS AND RESULTS: From soybean rhizosphere soil, 48 strains were isolated. Among them, the strain DR11 exhibited the highest inhibition rate of 72.27%. Morphological, physiological, biochemical, and 16S rDNA identification revealed that the strain DR11 was Klebsiella grimontii DR11. Strain DR11 could inhibit the growth of F. oxysporum and spore formation and alter the mycelial morphology. At 5.0 × 106 CFU mL-1, pH 7, and 30°C, it exhibited the highest inhibitory rate (72.27%). Moreover, it could decrease the activity of cell-wall-degrading enzymes of F. oxysporum. Simultaneously, the activities of defense-related enzymes and content of malondialdehyde in soybean plants were increased after treatment with strain DR11. In addition, strain DR11 could form aggregates to form biofilm and adsorb on the surface of soybean roots. It inhibited F. oxysporum growth on soybean seedlings, with an inhibitory effect of 62.71%. CONCLUSION: Klebsiella grimontii DR11 had a strong inhibitory effect on F. oxysporum and could be used as a biocontrol agent to combat F. oxysporum infection in soybean.

Synthesis and evaluation of novel pleuromutilin derivatives targeting the 50S ribosomal subunit for antibacterial ability.

Multidrug-resistant bacteria, particularly methicillin-resistant Staphylococcus aureus, have become a major global public health concern. Therefore, developing new antibiotics that do not possess cross-resistance for the currently available antibiotics is critical. Herein, we synthesized a novel class of pleuromutilin derivatives containing substituted triazine with improved antibacterial activity. Among these derivatives, 6d, which contains 4-dimethylamino-1,3,5-triazine in the side chain of pleuromutilin, exhibited highly promising antimicrobial activity and mitigated antibiotic resistance. The high antibacterial potency of 6d was further supported by docking model analysis and green fluorescent protein inhibition assay. Additionally, cytotoxicity and acute oral toxicity evaluation and in vivo mouse systemic infection experiments revealed that 6d possessed tolerable toxicity and promising therapeutic efficacy.

Immunogenicity and safety of concomitant administration of the sabin-strain-based inactivated poliovirus vaccine, the diphtheria-tetanus-acellular pertussis vaccine, and measles-mumps-rubella vaccine to healthy infants aged 18 months in China.

OBJECTIVES: During the COVID-19 pandemic, there was a decline in vaccine coverage, and the implementation of combined vaccines and co-administration strategies emerged as potential solutions to alleviate this predicament. Our objective is to delve into the concurrent administration of the sabin-strain-based inactivated poliovirus vaccine (sIPV), the diphtheria-tetanus-acellular pertussis vaccine (DTaP), and measles-mumps-rubella vaccine (MMR), with the intention of bridging the evidentiary gap pertaining to vaccine co-administration in Chinese infants, and to ensure a safe and effective vaccination strategy, ultimately leading to an augmentation in immunization coverage. METHODS: This study was a follow-up trial of the "Immunogenicity and safety of concomitant administration of the sIPV with the DTaP vaccine in children: a multicenter, randomized, non-inferiority, controlled trial." Blood samples were collected on day 0 and day 30, and serum antibody levels were detected to measure antibody responses to each of the antigens. Local and systemic adverse events were monitored and compared among groups. This study is the first to fill the knowledge gap in China regarding the safe and effective combined vaccination of sIPV, DTaP, and MMR vaccines. RESULTS: The geometric mean titer of the poliovirus types I, II, and III neutralizing antibodies were 1060.22 (95% CI: 865.73-1298.39), 1537.06 (95% CI: 1324.27-1784.05), and 1539.10 (95% CI: 1296.37-1827.29) in group I on day 30; geometric mean titer of antibodies against DTaP and MMR in the simultaneous vaccination group was non-inferior to those in the DTaP alone and MMR alone group. Reporting rates of local and systemic adverse reactions were similar between groups and no serious adverse events were reported throughout the clinical study period. CONCLUSION: Co-administration of the sIPV, DTaP, and MMR was safe and did not impact immunogenicity, which would help to mitigate administrative costs and enhance vaccine coverage rates.

The Effect of Polymer Blends on the In Vitro Release/Degradation and Pharmacokinetics of Moxidectin-Loaded PLGA Microspheres.

To investigate the effect of polymer blends on the in vitro release/degradation and pharmacokinetics of moxidectin-loaded PLGA microspheres (MOX-MS), four formulations (F1, F2, F3 and F4) were prepared using the O/W emulsion solvent evaporation method by blending high (75/25, 75 kDa) and low (50/50, 23 kDa) molecular weight PLGA with different ratios. The addition of low-molecular-weight PLGA did not change the release mechanism of microspheres, but sped up the drug release of microspheres and drastically shortened the lag phase. The in vitro degradation results show that the release of microspheres consisted of a combination of pore diffusion and erosion, and especially autocatalysis played an important role in this process. Furthermore, an accelerated release method was also developed to reduce the period for drug release testing within one month. The pharmacokinetic results demonstrated that MOX-MS could be released for at least 60 days with only a slight blood drug concentration fluctuation. In particular, F3 displayed the highest AUC and plasma concentration (AUC0-t = 596.53 ng/mL·d, Cave (day 30-day 60) = 8.84 ng/mL), making it the optimal formulation. Overall, these results indicate that using polymer blends could easily adjust hydrophobic drug release from microspheres and notably reduce the lag phase of microspheres.

Natural Products: A Dependable Source of Therapeutic Alternatives for Inflammatory Bowel Disease through Regulation of Tight Junctions.

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), can affect the entire gastrointestinal tract and mucosal layer and lead to intestinal damage and intestinal dysfunction. IBD is an inflammatory disease of the gastrointestinal tract that significantly impacts public health development. Monoclonal antibodies and other synthetic medications are currently used to treat IBD, but they are suspected of producing serious side effects and causing a number of other problems with long-term use. Numerous in vitro and in vivo studies have shown that organic macromolecules from plants and animals have an alleviating effect on IBD-related problems, and many of them are also capable of altering enzymatic function, reducing oxidative stress, and inhibiting the production of cytokines and release of proinflammatory transcriptional factors. Thus, in this paper, the natural products with potential anti-IBD activities and their mechanism of action were reviewed, with a focus on the protective effects of natural products on intestinal barrier integrity and the regulation of tight junction protein expression and remodeling. In conclusion, the insights provided in the present review will be useful for further exploration and development of natural products for the treatment of IBD.

Anti-methicillin-resistant Staphylococcus aureus activity and safety evaluation of 14-O-[(5-ethoxycarbonyl-4,6-dimethylpyrimidine-2-yl) thioacetyl] mutilin (EDT).

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have threated the public health worldwide, which emphasizes the urgent need for new drugs with novel mechanism of actions. 14-O-[(5-ethoxycarbonyl-4,6-dimethylpyrimidine-2-yl) thioacetyl] mutilin (EDT) is a pleuromutilin compound with high activity against several Gram-positive bacteria in vitro and in vivo. This study aimed to verifying the potential anti-MRSA activity and evaluating the safety of EDT. In in vitro antibacterial activity assays, EDT exhibited potent antibacterial activity against MRSA isolated from clinic (minimum inhibitory concentration = 0.0313-0.125 µg/mL), increased post-antibiotic effect (PAE) values and limited potential for the development of resistance. Docking model and green fluorescent protein (GFP) inhibition assay further elucidated the higher antibacterial activities of EDT via mechanism of action. In safety evaluation, EDT exhibited low cytotoxic effect and acute oral toxicity in mice and avoided to significantly increase the number of revertant colonies of six tested strains in the Ames study. Furthermore, EDT displayed a moderate inhibitory effect on CYP3A4 and moderate stability in mouse and human liver microsomes, providing a promising agent for the development of new antimicrobial candidate.