Bioguided isolation, identification and bioactivity evaluation of anti-fatigue constituents from Schizophyllum commune.

This study aims to clarify the specific anti-fatigue components of Schizophyllum commune (S.commune) and analyze its potential anti-fatigue mechanism. The main anti-fatigue active ingredient of S.commune was locked in n-butanol extract (SPE-n) by activity evaluation. Twelve compounds were identified by high performance liquid chromatography-electrospray tandem mass spectrometry (LC-ESI-MS/MS). The anti-fatigue effect of morusin is the most predominant among these 12 ingredients. The determination of biochemical indices showed that morusin could increase liver glycogen reserves, improve the activity of antioxidant enzymes in liver, and reduce reactive oxygen species (ROS) content in muscle tissue, thereby reducing myocyte damage. Further studies revealed that morusin could reduce the level of oxidative stress by activating Nrf2/HO-1 pathway, thus alleviating the fatigue of mice caused by exhaustive exercise. The current findings provide a theoretical basis for the development of natural anti-fatigue functional food.

Attenuation effect of a polysaccharide from large leaf yellow tea by activating autophagy.

Chemotherapy, the most common class of anticancer drugs, is considerably limited owing to its adverse side effects. In this study, we aimed to evaluate the protective effect and mechanism of action of large-leaf yellow tea polysaccharides (ULYTP-1, 1.29 × 104 Da) against chemotherapeutic 5-fluorouracil (5-Fu). Structural characterisation revealed that ULYTP-1 was a ß-galactopyranouronic acid. Furthermore, ULYTP-1 promoted autolysosome formation, activating autophagy and reducing the oxidative stress and inflammation caused by 5-Fu. Our in vivo study of 4 T1 tumour-bearing mice revealed that ULYTP-1 also attenuated 5-Fu toxicity through modulation of the gut microbiota. Moreover, ULYTP-1 effectively protected immune organs and the liver from 5-Fu toxicity, while promoting its tumour-inhibitory properties. The current findings provide a new strategy for optimising chemotherapy regimens in the clinic.

Amelioration of obesity and inflammation by polysaccharide from unripe fruits of raspberry via gut microbiota regulation.

Raspberry, a traditional medicine food homology species, has important benefits in patients with metabolic syndrome. However, the mechanism of raspberry polysaccharides (RP) on obesity remains unclear. In our study, we showed that RP intervention is negatively associated with body weight gain, hyperlipidemia, inflammation, and fat accumulation in obese mice. RP ameliorated HFD-induced gut microbiota dysbiosis, produced short-chain fatty acids, maintained intestinal barrier integrity, and prevented metabolic endotoxemia, manifested by decreased host lipopolysaccharide level, and increased colon expression of tight junction proteins. These effects might be related with driven by a SCFAs-producing bacterium and downregulation of TLR4/NF-κB signaling transduction. Notably, the abundance of Ruminococcaceae_UCG - 014, Lactobacillus taiwanensis, Bifidobacterium pseudolongum, and Turicibacter are markedly correlated with enhanced intestinal barrier function induced by RP treatment. Thus, we believe that RP could be as a potential health supplement or prebiotic for obesity therapy.

A new perspective on gut-lung axis affected through resident microbiome and their implications on immune response in respiratory diseases.

The highly diverse microbial ecosystem of the human body colonizes the gastrointestinal tract has a profound impact on the host's immune, metabolic, endocrine, and other physiological processes, which are all interconnected. Specifically, gut microbiota has been found to play a crucial role in facilitating the adaptation and initiation of immune regulatory response through the gastrointestinal tract affecting the other distal mucosal sites such as lungs. A tightly regulated lung-gut axis during respiratory ailments may influence the various molecular patterns that instructs priming the disease severity to dysregulate the normal function. This review provides a comprehensive summary of current research on gut microbiota dysbiosis in respiratory diseases including asthma, pneumonia, bronchopneumonia, COPD during infections and cancer. A complex-interaction among gut microbiome, associated metabolites, cytokines, and chemokines regulates the protective immune response activating the mucosal humoral and cellular response. This potential mechanism bridges the regulation patterns through the gut-lung axis. This paper aims to advance the understanding of the crosstalk of gut-lung microbiome during infection, could lead to strategize to modulate the gut microbiome as a treatment plan to improve bad prognosis in various respiratory diseases.

Whole-brain spatial organization of hippocampal single-neuron projectomes.

Mapping single-neuron projections is essential for understanding brain-wide connectivity and diverse functions of the hippocampus (HIP). Here, we reconstructed 10,100 single-neuron projectomes of mouse HIP and classified 43 projectome subtypes with distinct projection patterns. The number of projection targets and axon-tip distribution depended on the soma location along HIP longitudinal and transverse axes. Many projectome subtypes were enriched in specific HIP subdomains defined by spatial transcriptomic profiles. Furthermore, we delineated comprehensive wiring diagrams for HIP neurons projecting exclusively within the HIP formation (HPF) and for those projecting to both intra- and extra-HPF targets. Bihemispheric projecting neurons generally projected to one pair of homologous targets with ipsilateral preference. These organization principles of single-neuron projectomes provide a structural basis for understanding the function of HIP neurons.

Amelioration of Acute Alcoholic Liver Injury via Attenuating Oxidative Damage and Modulating Inflammation by Means of Ursodeoxycholic Acid-Zein Nanoparticles.

Ursodeoxycholic acid (UDCA) has been broadly adopted for the clinical treatment of hepatic and biliary diseases; however, its poor water-solubility becomes an obstacle in wide applications. To overcome these challenges, herein, a two-tier UDCA-embedded system of zein nanoparticles (NPs) along with a polyelectrolyte complex was designed under facile conditions. Both the UDCA-zein NPs and their inclusion microcapsules showed a spherical shape with a uniform size. A typical wall plus capsule/core structure was formed in which UDCA-zein NPs distributed evenly in the interior. The UDCA inclusion microcapsules had an encapsulation rate of 67% and were released in a non-Fickian or anomalous transport manner. The bioavailability and efficacy of UDCA-zein NPs were assessed in vivo through the alcoholic liver disease (ALD) mouse model via intragastric administration. UDCA-zein NPs ameliorated the symptoms of ALD mice remarkably, which were mainly exerted through attenuation of antioxidant stress levels. Meanwhile, it notably upregulated the intestinal tight junction protein expression and improved and maintained the integrity of the mucosal barrier effectively. Collectively, with the improvement of bioavailability, the UDCA-zein NPs prominently alleviated the oxidative damage induced by alcohol, modulating the inflammation so as to restore ALD. It is anticipated that UDCA-zein NPs have great therapeutic potential as sustained-nanovesicles in ALD treatment.

Deep Learning Performance of Ultra-Widefield Fundus Imaging for Screening Retinal Lesions in Rural Locales.

Importance: Retinal diseases are the leading cause of irreversible blindness worldwide, and timely detection contributes to prevention of permanent vision loss, especially for patients in rural areas with limited medical resources. Deep learning systems (DLSs) based on fundus images with a 45° field of view have been extensively applied in population screening, while the feasibility of using ultra-widefield (UWF) fundus image-based DLSs to detect retinal lesions in patients in rural areas warrants exploration. Objective: To explore the performance of a DLS for multiple retinal lesion screening using UWF fundus images from patients in rural areas. Design, Setting, and Participants: In this diagnostic study, a previously developed DLS based on UWF fundus images was used to screen for 5 retinal lesions (retinal exudates or drusen, glaucomatous optic neuropathy, retinal hemorrhage, lattice degeneration or retinal breaks, and retinal detachment) in 24 villages of Yangxi County, China, between November 17, 2020, and March 30, 2021. Interventions: The captured images were analyzed by the DLS and ophthalmologists. Main Outcomes and Measures: The performance of the DLS in rural screening was compared with that of the internal validation in the previous model development stage. The image quality, lesion proportion, and complexity of lesion composition were compared between the model development stage and the rural screening stage. Results: A total of 6222 eyes in 3149 participants (1685 women [53.5%]; mean [SD] age, 70.9 [9.1] years) were screened. The DLS achieved a mean (SD) area under the receiver operating characteristic curve (AUC) of 0.918 (0.021) (95% CI, 0.892-0.944) for detecting 5 retinal lesions in the entire data set when applied for patients in rural areas, which was lower than that reported at the model development stage (AUC, 0.998 [0.002] [95% CI, 0.995-1.000]; P < .001). Compared with the fundus images in the model development stage, the fundus images in this rural screening study had an increased frequency of poor quality (13.8% [860 of 6222] vs 0%), increased variation in lesion proportions (0.1% [6 of 6222]-36.5% [2271 of 6222] vs 14.0% [2793 of 19 891]-21.3% [3433 of 16 138]), and an increased complexity of lesion composition. Conclusions and Relevance: This diagnostic study suggests that the DLS exhibited excellent performance using UWF fundus images as a screening tool for 5 retinal lesions in patients in a rural setting. However, poor image quality, diverse lesion proportions, and a complex set of lesions may have reduced the performance of the DLS; these factors in targeted screening scenarios should be taken into consideration in the model development stage to ensure good performance.

Combinatorial gene therapy for epilepsy: Gene sequence positioning and AAV serotype influence expression and inhibitory effect on seizures.

Gene therapy with AAV vectors carrying genes for neuropeptide Y and its receptor Y2 has been shown to inhibit seizures in multiple animal models of epilepsy. It is however unknown how the AAV serotype or the sequence order of these two transgenes in the expression cassette affects the actual parenchymal gene expression levels and the seizure-suppressant efficacy. To address these questions, we compared three viral vector serotypes (AAV1, AAV2 and AAV8) and two transgene sequence orders (NPY-IRES-Y2 and Y2-IRES-NPY) in a rat model of acutely induced seizures. Wistar male rats were injected bilaterally with viral vectors and 3 weeks later acute seizures were induced by a subcutaneous injection of kainate. The latency until 1st motor seizure, time spent in motor seizure and latency to status epilepticus were measured to evaluate the seizure-suppressing efficacy of these vectors compared to an empty cassette control vector. Based on the results, the effect of the AAV1-NPY-IRES-Y2 vector was further investigated by in vitro electrophysiology, and its ability to achieve transgene overexpression in resected human hippocampal tissue was evaluated. The AAV1-NPY-IRES-Y2 proved to be better to any other serotype or gene sequence considering both transgene expression and ability to suppress induced seizures in rats. The vector also demonstrated transgene-induced decrease of glutamate release from excitatory neuron terminals and significantly increased both NPY and Y2 expression in resected human hippocampal tissue from patients with drug-resistant temporal lobe epilepsy. These results validate the feasibility of NPY/Y2 receptor gene therapy as a therapeutic opportunity in focal epilepsies.

Crystal-by-Crystal Assembly in Two Types of Periodically Banded Aggregates of Poly(p-Dioxanone).

The exterior and interior lamellar assemblies of poly(p-dioxanone) (PPDO) crystallized at 76 °C yield the most regular ones to interpret the 3D assembly mechanisms and potential for structural coloration iridescence, which are investigated using atomic-force microscopy (AFM), and scanning electron microscopy (SEM). PPDO displays two types of ring-banded spherulites within a range of Tc with dual-type birefringent spherulites (positive and negative-type) only within a narrow range of Tcs = 70−78 °C. At Tc > 80 °C, the inter-band spacing decreases from a maximum and the crystal assembly becomes irregularly corrupted and loses the capacity for light interference. Periodic grating assemblies are probed by in-depth 3D dissection into periodically banded crystal aggregates of poly(p-dioxanone) (PPDO) to disclose such layered gratings possessing iridescence features similar to nature's structural coloration. This work amply demonstrates that grating assembly by orderly stacked crystal layers is feasible not only for accounting for the periodic birefringent ring bands with polarized light but also the distinct iridescence by interfering with white light.

Effect of balance training on aerobics teaching for university students / Efeito do treinamento de equilíbrio no ensino de aeróbica para universitários / Efecto del entrenamiento de equilibrio en la enseñanza del aeróbic a estudiantes universitarios

ABSTRACT Introduction: Among the known benefits of aerobics gymnastics are flexibility, motor coordination improvement, weight loss, and balance improvement. The balance capacity is very important for aerobics students, and it is believed that introducing a complementary protocol can bring greater benefits to the performance of its practitioners. Objective: Explore the effects of balance training on university students practicing aerobics. Methods: A 9-week experiment was conducted employing 100 college aerobics students. The volunteers were divided into two groups without statistical differences. Balance training was added to the experimental group, while the control group remained with daily teaching practice. Results: The push-up score increased from 2.27±0.45 to 2.73±0.46, the body rotation score was from 1.87±0.35 to 2.40±0.51, and the squat score was from 2.53±0.52 to 3.03±0.30. While the aerobic ability of college students in the experimental group was effectively improved, no significant changes were observed in the control group data. Conclusion: Balance training can effectively improve college students' ability, leading to improvement in teaching aerobics to college students. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: Entre os benefícios da ginástica aeróbica conhecidos estão a flexibilidade, aprimoramento da coordenação motora, perda de peso, e a melhora no equilíbrio. A capacidade de equilíbrio é muito importante para os estudantes de aeróbica e acredita-se que a introdução de um protocolo complementar possa trazer maiores benefícios no desempenho de seus praticantes. Objetivo: Explorar os efeitos do treinamento de equilíbrio em estudantes universitários praticantes de aeróbica. Métodos: Uma experiência de 9 semanas foi realizada empregando 100 estudantes universitários de aeróbica, os voluntários foram divididos em dois grupos sem diferenças estatísticas. Ao grupo experimental foi adicionado um treino de equilíbrio, enquanto o grupo de controle permaneceu com a prática de ensino cotidiana. Resultados: A pontuação no push-up elevou-se de 2,27±0.45 para 2,73±0,46, a pontuação da rotação corporal foi de 1,87±0,35 para 2,40±0,51, e a pontuação em agachamento foi de 2,53±0,52 para 3,03±0,30. Enquanto a habilidade aeróbica dos estudantes universitários no grupo experimental foi efetivamente aperfeiçoada, não foram observadas alterações significativas nos dados do grupo de controle. Conclusão: O treinamento de equilíbrio pode efetivamente melhorar a habilidade dos estudantes universitários, conduzindo à melhoria do processo de ensino de aeróbica para universitários. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: Entre los beneficios conocidos de la gimnasia aeróbica están la flexibilidad, mejora de la coordinación motora, pérdida de peso, y el progreso en el equilibrio. La capacidad de equilibrio es muy importante para los alumnos de aeróbic y se cree que la introducción de un protocolo complementario puede aportar más beneficios en el rendimiento de sus practicantes. Objetivo: Explorar los efectos del entrenamiento del equilibrio en estudiantes universitarios que practican aeróbic. Métodos: Se realizó un experimento de 9 semanas en el que participaron 100 estudiantes universitarios de aeróbic, los voluntarios se dividieron en dos grupos sin diferencias estadísticas. Se añadió entrenamiento de equilibrio al grupo experimental, mientras que el grupo de control permaneció con la práctica docente diaria. Resultados: La puntuación de la flexión de brazos aumentó de 2,27±0,45 a 2,73±0,46, la puntuación de la rotación corporal fue de 1,87±0,35 a 2,40±0,51, y la puntuación de la sentadilla fue de 2,53±0,52 a 3,03±0,30. Mientras que la capacidad aeróbica de los estudiantes universitarios del grupo experimental mejoró eficazmente, no se observaron cambios significativos en los datos del grupo de control. Conclusión: El entrenamiento del equilibrio puede mejorar eficazmente la capacidad de los estudiantes universitarios, lo que conduce a la mejora del proceso de enseñanza del aeróbic para estudiantes universitarios. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Serum sulfatide as a biomarker of carotid atherosclerosis in patients with rheumatoid arthritis.

PURPOSE: Rheumatoid arthritis (RA) patients have accelerated atherosclerosis (AS) leading to excess cardiovascular morbidity and mortality, but traditional risk factors for cardiovascular disease (CVD) are invalid to explain the problem. Sulfatides, as major components of serum lipoproteins, are synthesized in the liver. These molecules are reported to play an important role in the development of AS, thrombogenesis, and inflammation. However, it is unclear whether sulfatides are responsible for such issue. To elucidate the possible association between serum sulfatide and the accelerated progress of AS, evaluated by carotid intima-media thickness (CIMT), and ascertain the related mechanism underlying the correlation in RA cases. METHODS: We performed an observational study of 144 patients with RA and 120 sex and age-matched controls. Meanwhile, 107 patients (of the 144 RA patients enrolled at baseline) were invited to undergo a second measurement after 12 months. Serum sulfatide levels of all the enrolled subjects were quantified by mass spectrometry after they were converted into lysosulfatides (LS), and then calculated as the sum of the levels of seven LS molecular species. Serum oxidative stress marker, malondialdehyde (MDA) was detected by ELISA. We subsequently statistically analyzed the causalities between carotid AS and clinical parameters, and the association of serum sulfatide with other variables. Multivariable logistic regression analysis was finally employed by taking all factors to identify independent determinant for carotid atherosclerotic plaque and serum sulfatide level. RESULTS: A gradual declined trend in serum sulfatide levels was observed in control subjects, non-plaque group, and the plaque group (8.56 ± 1.37 nmol/mL, 5.63 ± 1.57 nmol/mL, 3.18 ± 1.32 nmol/mL, respectively, p < 0.01), along with an increased value of CIMT (0.63 ± 0.07 mm, 0.92 ± 0.14 mm, 1.43 ± 0.22 mm, respectively, p < 0.01). Meanwhile, a negative linear correlation between CIMT and serum sulfatide was further confirmed by Spearman's analysis (r = -0.622, p < 0.01). Eventually, multivariate logistic regression analysis identified serum MDA as the only independent factor for the abnormal level of serum sulfatide, and serum sulfatide was detected as a significant protective factor for the occurrence of carotid plaques in RA cases (p < 0.01), which was confirmed repeatedly by our cross-sectional and longitudinal studies. CONCLUSION: Excessive abnormal levels of oxidative stress decreased serum sulfatide levels, followed by a high occurrence of AS in RA patients. Serum sulfatide level might be useful as a predictor (biomarker) for the progression of AS in RA cases.

Extraction, purification, structural characterization, and gut microbiota relationship of polysaccharides: A review.

Intestinal dysbiosis is one of the major causes of the occurrence of metabolic syndromes, such as obesity, diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Polysaccharide-based microbial therapeutic strategies have excellent potential in the treatment of metabolic syndromes, but the underlying regulatory mechanisms remain elusive. Identification of the internal regulatory mechanism of the gut microbiome and the interaction mechanisms involving bacteria and the host are essential to achieve precise control of the gut microbiome and obtain valuable clinical data. Polysaccharides cannot be directly digested; the behavior in the intestinal tract is considered a "bridge" between microbiota and host communication. To provide a relatively comprehensive reference for researchers in the field, we will discuss the polysaccharide extraction and purification processes and chemical and structural characteristics, focusing on the polysaccharides in gut microbiota through the immune system, gut-liver axis, gut-brain axis, energy axis interactions, and potential applications.

Sorafenib-Loaded PLGA-TPGS Nanosystems Enhance Hepatocellular Carcinoma Therapy Through Reversing P-Glycoprotein-Mediated Multidrug Resistance.

Multidrug resistance (MDR) is a key determinant for hepatocellular carcinoma chemotherapy failure. P-glycoprotein is one of the main causes of MDR by causing drug efflux in tumor cells. In order to solve this thorny problem, we prepared a sorafenib-loaded polylactic acid-glycolic acid (PLGA) - D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) nanoparticles (SPTNs). SPTNs were successfully synthesized through an ultrasonic emulsion solvent evaporation method with a favourable encapsulation efficiency of 90.35%. SPTNs were almost spherical in shape with uniform particle size (215.70 ± 0.36 nm), narrow polydispersity index (0.27 ± 0.02) and negative surface charge (-26.01 ± 0.65 mV). In the cellular uptake assay, the intracellular coumarin-6 (C6) fluorescence of TPGS component-based PLGA nanoparticles (C6-PTNs) was 1.63-fold higher relative to that of PVA component-based PLGA nanoparticles (C6-PVNs). The half-maximal inhibitory concentration and apoptosis ratio of SPTNs against HepG2/MDR cells were 3.90 µM and 75.62%, respectively, which were notably higher than free SF and sorafenib-PLGA-PVA nanoparticles (SPVNs). The anti-drug efflux activities of SPTNs were assessed by the intracellular trafficking assay using verapamil as a P-gp inhibitor. SPTNs could effectively inhibit the drug efflux in tumor cells detected by flow cytometry, and suppressed relative MDR1 gene as well as P-glycoprotein expression in tumor cells. Attributed to the MDR reversion effect of SPTNs, the in vivo antitumor efficacy experiment showed that SPTNs significantly inhibited the tumor growth of HepG2/MDR xenograft-bearing nude mice, and obviously reduced the toxicity against liver and kidney compared with SF treatment. In summary, SPTNs, as highly efficient and safe antitumor nano delivery systems, showed promising potential for hepatocellular carcinoma therapy through reversing P-glycoprotein-mediated MDR. Graphical Abstract.

[Discussion on Supervision and Sampling of Biochemical Test Kits].

As an important part of medical devices, in vitro diagnostic reagents are important means to prevent and diagnose and protect people's health. Supervision and sampling is an important and key supervision method to ensure the in vitro diagnostic reagent products are qualified. This paper summarizes the problems encountered in recent years in vitro diagnostic quantitative testing kit supervision sampling, analyzes the causes of these problems, and puts forward corresponding suggestions, hoping to provide constructive suggestions for supervision sampling.

Effects of ultra-high pressure treatment on structure and bioactivity of polysaccharides from large leaf yellow tea.

In this study, the changes of structure and bioactivity of polysaccharides from large leaf yellow tea (LYTP) were investigated under ultra-high pressure (UHP). Native yellow tea polysaccharide were treatmented with ultra-high pressure (200, 400 and 600 MPa) for 5 min to yield yellow tea polysaccharide including 200 MPa-LYTP, 400 MPa-LYTP and 600 MPa-LYTP. It was found that the monosaccharide composition of LYTP changed significantly after the ultra-high pressure treatment. The molecular weight (Mw) of 200 MPa-LYTP (from 563.6 to 11.7 kDa), 400 MPa-LYTP (from 372.2 to 11.8 kDa) and 600 MPa-LYTP (from 344 to 11.6 kDa) sharply decreased upon ultra-high pressure treatment compared with LYTP (771.5 kDa), coincidentally particle size was also significantly reduced for 200 MPa-LYTP (23.2 %), 400 MPa-LYTP (40.2 %) and 600 MPa-LYTP (25.9 %). The results of the scanning electron microscope showed that ultra-high pressure also changed the surface and spatial morphology of LYTP. LYTP after ultra-high pressure treatment (UHP-LYTP) could further ameliorate alcohol-induced liver injury in mice. In addition, UHP treatment can more efficiently remove protein than the Sevages method. With the gradual removal of protein, its hepatoprotective effect increased. These findings demonstrated that UHP treatment could change the primary structure and spatial structure of LYTP, increase the content of acidic polysaccharides, and improve its bioactivity.

Antibacterial effect and mechanism against Escherichia coli of polysaccharides from Armillariella tabescens mycelia.

The objectives of this study were (1) to prepare Armillariella tabescens mycelia polysaccharides (PAT) with remarkably growth inhibitory effect on typical food-borne pathogenic bacteria using a green and efficient polyamide method and (2) to explore the antibacterial mechanism of PAT for use as a natural antibacterial agent. The sugar and uronic acid contents of PAT were 93.41% and 12.24%, respectively. PAT could inhibit the growth of Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Staphylococcus aureus cells, with minimum inhibitory concentrations of 0.5, 1.0, 4.0, and 4.0 mg/mL, respectively. Ultra-high-resolution field emission scanning electron microscopy and high-resolution transmission electron microscopy analysis revealed cell wall and membrane rupture of E. coli treated with PAT. Further, 0.5-4.0 mg/mL PAT was found to significantly (P < 0.01) and concentration-dependently increase the conductivity of the broth, exudation of the intracellular protein, and alkaline phosphatase and ß-galactosidase activities. Confocal laser scanning microscopy revealed morphological changes in E. coli DNA after PAT treatment and intracellular reactive oxygen species accumulation; flow cytometry revealed E. coli cell apoptosis. Our findings provide a theoretical basis and technical support for the development of PAT as a natural antibacterial product.

[Determination Methods of 2019 Novel Coronavirus (SARS-CoV-2)].

This study summarized the determination methods and principles of 2019 novel coronavirus(severe acute respiratory syndrome coronavirus 2,SARS-CoV-2). The advantages and limitations of several methods was compared, which can provide a basis for the selection of 2019 novel coronavirus clinical diagnosis methods.

Polysaccharides from Armillariella tabescens mycelia ameliorate renal damage in type 2 diabetic mice.

Diabetic kidney disease (DKD), accompanied by chronic low-grade inflammation, is one of the most common complications of diabetes. Armillariella tabescens has potent anti-inflammatory and immunomodulatory properties. The purpose of the present study was to investigate the effects of polysaccharides from Armillariella tabescens mycelia (AT) on the kidney in type 2 diabetic mice and explore the underlying mechanism. The mice were randomized into 4 groups: normal control (NC), diabetic control (DC), DC + 200 mg/kg AT (LAT), and DC + 400 mg/kg AT (HAT). The results showed that compared with the NC group, the levels of fasting blood glucose, renal function-related indices, and serum pro-inflammatory mediators including lipopolysaccharide (LPS), interleukin (IL)-1ß, and IL-18 were elevated; the renal morphopathological alterations, oxidative stress, and nucleotide-binding oligomerization domain-like receptor protein 3 inflammasome-mediated inflammation and renal fibrosis were aggravated; the intestinal microbiota dysbiosis and colonic inflammation and barrier dysfunction were deteriorated in the DC group. After supplementation with AT, the aforementioned indices were ameliorated in the AT treatment groups, especially in the HAT group. In conclusion, these results demonstrated that modulating the intestinal microbiota and inflammatory reaction was implicated in the effects of AT against DKD in mice.

Solid dispersion-based pellet for colon delivery of tacrolimus through time- and pH-dependent layer coating: preparation, in vitro and in vivo studies

The intent of the present investigation is to develop and evaluate colon-specific coated tacrolimus solid dispersion pellet (SDP) that retards drug release in the stomach and small intestine but progressively releases in the colon. Tacrolimus-SDP was prepared by extrusion-spheronization technology and optimized by the micromeritic properties including flowability, friability, yields and dissolution rate. Subsequently, the pH-dependent layer (Eudragit L30D55) and time-dependent layer (Eudragit NE30D and L30D55) were coated on the SDP to form tacrolimus colon-specific pellets (CSP) using a fluidized bed coater. Under in vitro gradient pH environment, tacrolimus only released from CSP after changing pH to 6.8 and then quickly released in the phosphate buffer solution of pH 7.2. The Cmax of CSP was 195.68 ± 3.14 ng/mL at Tmax 4.5 ± 0.24 h where as in case of SDP, the Cmax was 646.16 ± 8.15 ng/mL at Tmax 0.5 ± 0.03 h, indicating the ability of CSP targeted to colon. The highest area under the curve was achieved 2479.58 ± 183.33 ng·h/mL for SDP, which was 2.27-fold higher than tacrolimus suspension. However, the best biodistribution performance was achieved from CSP. In conclusion, SDP combining of pH- and time-dependent approaches was suitable for targeted delivery of tacrolimus to colon.

Orally targeted galactosylated chitosan poly(lactic-co-glycolic acid) nanoparticles loaded with TNF-ɑ siRNA provide a novel strategy for the experimental treatment of ulcerative colitis.

The current treatments used in inflammatory bowel disease (IBD) therapy have significant side effects. Thus, it is very necessary to position and release TNF-α siRNA in inflamed tissues. Here, we demonstrate that poly(lactic-co-glycolic acid) can pack TNF-α siRNA efficiently into nanoparticles (NPs), and galactosylated chitosan (GC) can be grafted onto the NP surface, improving the RAW 264.7 macrophage-targeting kinetics of the NPs in vitro. Next, we orally administered GC-modified NPs loaded with TNF-α siRNA to C57BL/6 mice treated with 3% dextran sodium sulfate (DSS) to investigate their use in the treatment of colitis. When TNF-α siRNA loaded NPs were released into the colitis tissues of mice, GC-modified NPs (GPNs) alleviated the inflammation more efficiently than unmodified PGLA NPs (PNs). A series of colitis parameters (e.g., weight loss, myeloperoxidase (MPO) activity) demonstrated that GPNs have better anti-inflammatory effects than PNs. As indicated by flow cytometry, grafting GC onto NPs increased the macrophage uptake capacity and improved the kinetics of endocytosis. Collectively, our findings indicate that GC- modified TNF-α siRNA loaded NPs are powerful and efficient nanoscale materials for the delivery of therapeutic molecules to colitis tissues.