Efficacy and safety of Oral LL-37 against the Omicron BA.5.1.3 variant of SARS-COV-2: A randomized trial.

Recombinant LL-37 Lactococcus lactis (Oral LL-37) was designed to prevent progression of COVID-19 by targeting virus envelope, however, effectiveness and safety of Oral LL-37 in clinical application was unclear. A total of 238 adult inpatients, open-labelled, randomized, placebo-controlled, single-center study was conducted to investigate the primary end points, including negative conversion time (NCT) of SARS-CoV-2 RNA and adverse events (AEs). As early as intervened on 6th day of case confirmed, Oral LL-37 could significantly shorten NCT (LL-37 9.80 ± 2.67 vs. placebo 14.04 ± 5.89, p < 0.01). For Oral LL-37, as early as treated in 6 days, the adjusted hazard ratio (HR) for a primary event of nucleic acid negative outcome was 6.27-fold higher than 7-day-later (HR: 6.276, 95% confidence interval [CI]: 3.631-10.848, p < 0.0001), and the adjusted HR of Oral LL-37 within 6 days is higher than placebo (HR: 2.427 95% CI: 1.239-4.751, p = 0.0097). No severe AEs were observed during hospitalization and follow-up investigation. This study shows that early intervention of Oral LL-37 incredibly reduces NCT implying a potential for clearance of Omicron BA.5.1.3 without evident safety concerns.

[Three new cucurbitane-type triterpenoid glycosides from Citrullus colocynthis and their anti-inflammatory activity].

Three new cucurbitane-type triterpenoid glycosides were separated from the ethyl acetate extract of Citrullus colocynthis by a variety of chromatographic techniques. According to the data of NMR, HR-ESI-MS, and/or comparison with the reported data, the three novel cucurbitane-type triterpenoid glycosides were identified as colocynthenin E(1), colocynthenin G(2), and colocynthenin H(3). The cell inflammation model was established with RAW264.7 macrophages exposed to lipopolysaccharide and then used to determine the anti-inflammatory activities of the three compounds. Compounds 2 and 3 showed mild anti-inflammatory activities with the IC_(50) of 48.21 and 40.11 µmol·L~(-1), respectively, compared with that(IC_(50)=7.57 µmol·L~(-1)) of the positive control dexamethasone.

Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome.

In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.

Two novel qualitative transcriptional signatures robustly applicable to non-research-oriented colorectal cancer samples with low-quality RNA.

Currently, due to the low quality of RNA caused by degradation or low abundance, the accuracy of gene expression measurements by transcriptome sequencing (RNA-seq) is very challenging for non-research-oriented clinical samples, majority of which are preserved in hospitals or tissue banks worldwide with complete pathological information and follow-up data. Molecular signatures consisting of several genes are rarely applied to such samples. To utilize these resources effectively, 45 stage II non-research-oriented samples which were formalin-fixed paraffin-embedded (FFPE) colorectal carcinoma samples (CRC) using RNA-seq have been analysed. Our results showed that although gene expression measurements were significantly affected, most cancer features, based on the relative expression orderings (REOs) of gene pairs, were well preserved. We then developed two REO-based signatures, which consisted of 136 gene pairs for early diagnosis of CRC, and 4500 gene pairs for predicting post-surgery relapse risk of stage II and III CRC. The performance of our signatures, which included hundreds or thousands of gene pairs, was more robust for non-research-oriented clinical samples, compared to that of two published concise REO-based signatures. In conclusion, REO-based signatures with relatively more gene pairs could be robustly applied to non-research-oriented CRC samples.

A qualitative transcriptional signature of recurrence risk for stages II-III gastric cancer patients after surgical resection.

BACKGROUND AND AIM: Metastasis is the leading cause of recurrence in gastric cancer. However, the imaging techniques and pathological examinations for tumor metastasis have a high false-positive rate or a high false-negative rate, and many proposed that metastasis-related molecular biomarkers can hardly be validated in independent datasets. METHODS: We propose to use significantly stable gene pairs with reversal relative expression orderings (REOs) between non-metastasis and metastasis gastric cancer samples as the metastasis-related gene pairs. Based on the REOs of these gene pairs, we developed a qualitative transcriptional signature for predicting the recurrence risk of stages II-III gastric cancer patients after surgical resection. RESULTS: A REOs-based signature, consisting of 19 gene pairs (19-GPS), was selected from 77 stages II-III gastric cancer patients and validated in two independent datasets. Samples in the high-risk group had shorter disease-free survival time and overall survival time than those in the low-risk group. Differentially expressed genes (DEGs) between the high- and low-risk groups classified by 19-GPS were highly reproducible comparing with those between lymph node metastasis and lymph node non-metastasis groups. Functional enrichment analysis showed that these DEGs were significantly enriched in metastasis-related pathways, such as PI3K-Akt and Rap1 signaling pathways. The multi-omics analyses suggested that the epigenetic and genomic features might cause transcriptional differences between two subgroups, which help to characterize the mechanism of gastric cancer metastasis. CONCLUSIONS: The signature could robustly identify patients at high recurrence risk after resection surgery, and the multi-omics analyses might aid in revealing the metastasis-related characteristics of gastric cancer.

Effects of air-abrasion pressure on mechanical and bonding properties of translucent zirconia.

OBJECTIVES: The purpose of this in vitro study was to investigate the effects of different air-abrasion pressures on flexural strength and shear bond strength of a translucent zirconia. MATERIALS AND METHODS: The translucent zirconia surface was treated with 50 µm abrasive alumina particles at different pressure: 0.1 MPa; 0.2 MPa; 0.3 MPa; 0.4 MPa; 0.5 MPa; untreated specimens were used as control group (n = 33). For each group, three-point bending test was used to evaluate the flexural strength, and surface characterizations were analyzed. Following adhesive bonding and water storage for 24 h, specimens were subdivided into groups baseline and aged (5000 thermocycles). Then, shear bond strength was measured and failure mode was recorded. Statistical analysis was performed with one-way ANOVA and Tukey test (α = 0.05). RESULTS: Increasing air-abrasion pressure (0.3 MPa, 0.4 MPa, and 0.5 MPa) decreased the flexural strength. Higher air-abrasion pressure resulted in rougher zirconia surfaces and caused more microcracks. The highest shear bond strength was obtained for zirconia surfaces abraded at 0.2 MPa (15.88 ± 2.70 MPa) and 0.3 MPa (14.32 ± 1.12 MPa). Aging did not decrease the strength for all groups except control group (p < 0.001). CONCLUSIONS: Air-abrasion with 50 µm abrasive alumina particles at 0.2 MPa could achieve good strength for translucent zirconia ceramics while maintaining adequate and durable bonding with resin cement. CLINICAL RELEVANCE: A total of 0.2 MPa is recommended for air-abrasion procedure applied before a dental restoration fabricated with translucent zirconia is bonded to resin cement.

Glass-ceramic resin-bonded fixed partial dentures for replacing a single premolar tooth: A prospective investigation with a 4-year follow-up.

STATEMENT OF PROBLEM: Resin-bonded fixed partial dentures (RBFPDs) are a reliable treatment option for the replacement of a single missing tooth. Glass-ceramic may be a promising material for the fabrication of RBFPDs, but clinical verification has been lacking. PURPOSE: The purpose of this prospective clinical study was to evaluate the outcomes of glass-ceramic RBFPDs on participants with a single missing premolar. MATERIAL AND METHODS: Twenty participants (6 men, 14 women; age range: 20 to 54 years) were treated with 2-retainer RBFPDs. These RBFPDs were made of lithium disilicate glass-ceramic (IPS e.max Press; Ivoclar Vivadent AG) and designed with improved C-shaped retention. These prostheses were evaluated at 6 months, 12 months, and annually thereafter and were classified as survival or failure. Analysis was performed with the Kaplan-Meier analysis (95% confidence interval). Modified United States Public Health Service (USPHS) criteria were used to rate the clinical performance. Parameters assessed were fracture, marginal integrity, marginal discoloration, color of restoration, secondary caries, and abutment mobility. RESULTS: Twenty RBFPDs were provided, 9 in the maxilla and 11 in the mandible. The mean observation time was 49.2 months (minimum 9 months, maximum 53 months). Nineteen RBFPDs were evaluated as having survived during the observation period with some acceptable marginal discoloration, 1 RBFPD had to be replaced because of fracture and secondary caries and was evaluated as a failure. The Kaplan-Meier analysis revealed a survival rate of 95% after a 4-year observation. CONCLUSIONS: The glass-ceramic RBFPDs in this study displayed a good survival rate and clinical performance, indicating that glass-ceramic RBFPDs might be a promising approach for the short-term replacement of a single premolar. However, further investigations are needed to determine the long-term outcome.

Novel Bioactive and Therapeutic Dental Polymeric Materials to Inhibit Periodontal Pathogens and Biofilms.

Periodontitis is a common infectious disease characterized by loss of tooth-supporting structures, which eventually leads to tooth loss. The heavy burden of periodontal disease and its negative consequence on the patient's quality of life indicate a strong need for developing effective therapies. According to the World Health Organization, 10⁻15% of the global population suffers from severe periodontitis. Advances in understanding the etiology, epidemiology and microbiology of periodontal pocket flora have called for antibacterial therapeutic strategies for periodontitis treatment. Currently, antimicrobial strategies combining with polymer science have attracted tremendous interest in the last decade. This review focuses on the state of the art of antibacterial polymer application against periodontal pathogens and biofilms. The first part focuses on the different polymeric materials serving as antibacterial agents, drug carriers and periodontal barrier membranes to inhibit periodontal pathogens. The second part reviews cutting-edge research on the synthesis and evaluation of a new generation of bioactive dental polymers for Class-V restorations with therapeutic effects. They possess antibacterial, acid-reduction, protein-repellent, and remineralization capabilities. In addition, the antibacterial photodynamic therapy with polymeric materials against periodontal pathogens and biofilms is also briefly described in the third part. These novel bioactive and therapeutic polymeric materials and treatment methods have great potential to inhibit periodontitis and protect tooth structures.

Effects of combined modification of sulfonation, oxygen plasma and silane on the bond strength of PEEK to resin.

OBJECTIVE: This study aimed to evaluate the combined effects of sulfonation, non-thermal oxygen plasma and silane on the shear bond strength (SBS) of PEEK to resin materials. MATERIALS AND METHODS: Two hundred and eighty specimens were randomly divided into four groups: (A) untreated; (B) sulfonation for 60 s; (C) oxygen plasma for 20 min; (D) sulfonation for 60 s and oxygen plasma for 20 min. According to the instructions, 120 samples (N = 30) were coated with silane, adhesive, and resin composites. Each group of bonding specimens was divided into two subgroups (n = 15) to measure immediate and post-aging SBS. The surface morphology and the interface between the samples and adhesive were analyzed through SEM. Physicochemical characteristics of the surface and mechanical properties were determined through XPS, FTIR, light interferometry, contact angle measurement, and three-point bending tests. RESULTS: Sulfonation produced a porous layer of approximately 20 µm thickness on the surface, and the oxygen plasma increased the O/C ratio and oxygen-containing groups of the sample surface. After coating with silane, the SBS values of sulfonated PEEK and plasma-treated PEEK increased (9.96 and 10.72 MPa, respectively), and dual-modified PEEK exhibited the highest SBS value (20.99 MPa), which was significantly higher than that of blank group (p > 0.01). After 10,000 thermal cycles, the dual-modified PEEK still displayed a favorable SBS (18.68 MPa). SIGNIFICANCE: Sulfonation strengthened the mechanical interlocking between PEEK and the resin while oxygen plasma established a chemical bonding between silane and PEEK. This dual modification of the surface microstructure and chemical state synergistically improved the bond strength of PEEK to resin and resulted in considerable long-term effects.

Multifunctional surface of the nano-morphic PEEK implant with enhanced angiogenic, osteogenic and antibacterial properties.

Polyetheretherketone (PEEK) is a high-performance polymer suitable for use in biomedical coatings. The implants based on PEEK have been extensively studied in dental and orthopedic fields. However, their inherent inert surfaces and poor osteogenic properties limit their broader clinical applications. Thus, there is a pressing need to produce a multifunctional PEEK implant to address this issue. In response, we developed sulfonated PEEK (sPEEK)-Cobalt-parathyroid hormone (PTH) materials featuring multifunctional nanostructures. This involved loading cobalt (Co) ions and PTH (1-34) protein onto the PEEK implant to tackle this challenge. The findings revealed that the controlled release of Co2+ notably enhanced the vascular formation and the expression of angiogenic-related genes, and offered antimicrobial capabilities for sPEEK-Co-PTH materials. Additionally, the sPEEK-Co-PTH group exhibited improved cell compatibility and bone regeneration capacity in terms of cell activity, alkaline phosphatase (ALP) staining, matrix mineralization and osteogenic gene expression. It surpassed solely sulfonated and other functionalized sPEEK groups, demonstrating comparable efficacy even when compared to the titanium (Ti) group. Crucially, animal experiments also corroborated the significant enhancement of osteogenesis due to the dual loading of cobalt ions and PTH (1-34). This study demonstrated the potential of bioactive Co2+ and PTH (1-34) for bone replacement, optimizing the bone integration of PEEK implants in clinical applications.

Impact of Oat Supplementation on the Structure, Digestibility, and Sensory Properties of Extruded Instant Rice.

The addition of oat at varying percentages (26%, 32%, 38%, 44% and 50%) was used to evaluate the structural, microstructural, and physicochemical changes in instant-extruded rice (IER). A mixture of broken rice and oat flour was extruded in a twin-screw extruder. It was found that when adding 44% oats, the gelatinization degree of the mixed powder was the lowest (89.086 ± 1.966%). The dietary fiber content increased correspondingly with the increase in oat addition. Analyses of texture properties revealed that the hardness, adhesive, and resilience values increased and then decreased with oat addition. Compared with other common instant rice (IR), the advantages of IER were evaluated in terms of microstructure, digestive performance, and flavor. IER with 44% oat addition obtained in this study had higher hardness, adhesiveness, rehydration time, and sensory score, and the content of resistant starch (RS) reached 6.06%. The electronic nose and electronic tongue analyses could distinguish the flavor of different IR efficiently. This study showed the feasibility of preparing fiber-enriched IER. The results demonstrated the potential for the development and utilization of broken rice, providing a reference for the development of IER.

A metagenomics study reveals the gut microbiome as a sex-specific modulator of healthy aging in Hainan centenarians.

BACKGROUND: Sex differences in health status and life expectancy are widely accepted to exist. The mechanisms underlying it are still poorly understood. In this study, we aimed to clarify the influences and contributions of sex on the gut microbiome in healthy centenarians and to explore the different roles played by the gut microbiome in healthy aging between the sexes. RESULTS: Taking covariates of different dimensions into account (social demographics, anthropometry, the activities of daily living, dietary structure, mental state, blood tests, lifestyle and disease history), our data showed that sex was one of the most significant covariates affecting the gut microbiome of healthy centenarians at both the species and Kyoto Encyclopedia of Genes and Genomes Orthology (KO) levels. The beta diversity between the sexes were significantly different (Adonis test: p = 0.011, R2 = 0.031), and the male centenarians had a greater alpha diversity than the females (Simpson and Shannon test: P<0.05). At the species level, we identified 31 species enriched in males and 7 species enriched in females. The composition and function patterns of the microbiome varied between the sexes. Further functional analysis showed that males' gut microbiome exhibited greater resistance to oxidative stress compared to females. In contrast to men, the species associated with healthy aging dominated among healthy female centenarians, while the species associated with unhealthy aging were relatively rare. CONCLUSIONS: The present study reveals that the gut microbiome structure and resistance to oxidative stress in healthy centenarians differ between the sexes and provides new insights into the possible sex-specific role of the gut microbiome in healthy aging.

Properties investigations of rape stalks fermented by different salt concentration: Effect of volatile compounds and physicochemical indexes.

In order to find out the effect of salt concentration on fermented rape stalks, the physicochemical quality and volatile components was investigated using high performance liquid chromatography (HPLC) and headspace solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS). The results showed that there were abundant kinds of free amino acids (FAAs) in all samples, mainly presenting sweet, umami and bitter taste. Through taste activity value (TAV), His, Glu, and Ala contributed significantly to the taste of the sample. 51 volatile components were identified, of which the relative contents of ketones and alcohols were high. By the relative odor activity value (ROAV) analysis, the main components that had a great impact on the flavor were phenylacetaldehyde, ß-Ionone, ethyl palmitate and furanone. Adjusting the appropriate salt concentration for fermentation could improve the comprehensive quality of fermented rape stalks and promote the development and utilization of rape products.

Effects of thermal cycling on bonding properties of novel low-shrinkage resin adhesive.

OBJECTIVES: The current study aimed to investigate the bonding properties of a novel low-shrinkage resin adhesive containing expanding monomer and epoxy resin monomer after thermal cycling aging treatment. METHODS: Expanding monomer of 3,9-diethyl-3,9-dimethylol-1,5,7,11-tetraoxaspiro-[5,5] undecane (DDTU) as an anti-shrinkage additive and unsaturated epoxy monomer of diallyl bisphenol A diglycidyl ether (DBDE) as a coupling agent were synthesized. A blend of DDTU and DBDE at a mass ratio of 1∶1, referred to as "UE", was added into the resin matrix at the mass fraction of 20% to prepare a novel low-shrinkage resin adhesive.Then, the methacrylate resin adhesive without UE was used as the blank control group, and a commercial resin adhesive system was selected as the commercial control group. Moreover, the resin-dentin bonding and micro-leakage testing specimens were prepared for the thermal cycling aging treatment. The bonding strength was tested, the fracture modes were calculated, the bonding fracture surface was observed by scanning electron microscope (SEM), and the dye penetration was used to evaluate the tooth-restoration marginal interface micro-leakage. All the data were analyzed statistically. RESULTS: After aging, the dentin bonding strength of the experimental group was (19.20±1.03) MPa without a significant decrease (P>0.05), that of the blank control group was (11.22±1.48) MPa with a significant decrease (P<0.05) and that of the commercial control group was (19.16±1.68) MPa without a significant decrease (P>0.05). The interface fracture was observed as the main fracture mode in each group after thermal cycling by SEM. The fractured bonding surfaces of the experimental group often occurred on the top of the hybrid layer, whereas those of the blank and commercial control groups mostly occurred on the bottom of the hybrid layer. Micro-leakage rating counts of specimens before and after thermal cycling were as follows: the experimental group was primarily 0 grade, thereby indicating that a relatively ideal marginal sealing effect could be achieved (P>0.05); meanwhile, the blank control group was primarily 1 grade, and the penetration depth of dye significantly increased after thermal cycling (P<0.05); the commercial control group was primarily 0 grade without statistical difference before and after thermal cycling (P>0.05), while a significant difference was observed between the commercial control group and experimental group after thermal cycling (P<0.05). CONCLUSIONS: The novel low-shrinkage resin adhesive containing 20%UE exhibited excellent bonding properties even after thermal cycling aging treatment, thereby showing a promising prospect for dental application.

Novel antimicrobial and self-healing dental resin to combat secondary caries and restoration fracture.

OBJECTIVE: Dental resin composites have been the most popular materials for repairing tooth decay in recent years. However, secondary caries and bulk fracture are the major hurdles that affect the lifetime of dental resin composites. This current study synthesized a novel antimicrobial and self-healing dental resin containing nanoparticle-modified self-healing microcapsules to combat secondary caries and restoration fracture. METHODS: Multifunctional dental resins containing 0-20% nanoparticle-modified self-healing microcapsules were prepared. The water contact angle, antimicrobial properties, mechanical properties, cell toxicity, and self-healing capability of the dental resins were tested. RESULTS: A novel multifunctional dental resin was synthesized. When the microcapsule mass fraction was 10%, the resin presented a strong bacteriostasis rate (80.3%) and excellent self-healing efficiency (66.1%), while the hydrophilicity, mechanical properties, and cell toxicity were not affected. SIGNIFICANCE: The novel antimicrobial self-healing dental resin is a promising candidate for use in clinical practice, which provides a simple and highly efficient strategy to combat secondary caries and restoration fracture. This novel dental resin also gives the inspiration to prolong the service life of dental restorations.

Novel low-shrinkage dental resin containing microcapsules with antibacterial and self-healing properties.

Dental resin restorations commonly fail because of fractures and secondary caries. The aim of this research was to synthesize a novel low-shrinkage dental resin with antibacterial and self-healing properties. The low-shrinkage dental resin was obtained by incorporating a 20 wt% anti-shrinkage mixture of an expanding monomer 3,9-diethyl-3,9-dimethylol -1,5,7,11-tetraoxaspiro[5,5] undecane and an epoxy resin monomer diallyl bisphenol A diglycidyl ether (1:1, referred as "UE") and different mass fractions of self-healing antibacterial microcapsules (0%, 2.5%, 5%, 7.5%, and 10%) were incorporated into the matrix to prepare multifunctional dental resin. Polymerization shrinkage, mechanical properties, antibacterial activity, self-healing ability, and cytotoxicity of this dental resin were evaluated. The polymerization volumetric shrinkage of resin containing 20 wt% UE and 7.5 wt% microcapsules was reduced by 30.12% (4.13% ± 0.42%) compared with control. Furthermore, it exhibited high antibacterial activity and a good self-healing efficiency of 71% without adversely affecting the mechanical property and cell viability. This novel multifunctional dental resin with low polymerization shrinkage and excellent antibacterial activity and self-healing capability has potential application as a dental resin material to decrease the incidence of fractures and secondary caries.

Xiangshao Granules reduce the aggressive behavior and hippocampal injury of premenstrual irritability in rats by regulating JIK/JNK/p38 signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: As a typical prescription for soothing the liver, Xiangshao granule has a good effect on the symptoms of irritability and anxiety. Clinical evidence suggests that it has significant efficacy in the treatment of Premenstrual dysphoria disorder (PMDD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: PMDD is a common disease in women of childbearing age, seriously affecting their family, society, and daily work life. The registered herbal medicine, Xiangshao granules, is used for relieving PMDD dysphoria and irritability symptoms with excellent efficacy in China. This study was focused on the deep intervention mechanism of Xiangshao granules in treating PMDD. MATERIALS AND METHODS: The vaginal smear and open field test were used to screen rats in nonreception phase of estrus cycle with similar macroscopic behaviors and regular estrus cycle. The rat model of PMDD irritability was established through social isolation and residential invasion, with which, the irritability symptoms of PMDD patients with menstrual cycle dependence was also well simulated. Elevated plus Maze Test and Social interaction activities were used to measure the anxiety-like behavior of rats. TUNEL Staining and Hematoxylin-Eosin staining were used to measure apoptosis of hippocampal neurons. RT-PCR, Western blot and immunofluorescence were used to measure the expression of GR, JIK, p-JIK, p38, P-P38, JNK, caspase 3, and caspase 12. RESULTS: In this study, Xiangshao granules showed consistent therapeutic effects similar with those in clinic, significantly reducing aggressive and anxiety-like behaviors with improved social skills in PMDD rats. In mechanism, Xiangshao granules lowered the apoptosis of hippocampal neurons and weakened the morphological damage of the hippocampal brain evidenced by the decreased mRNA and protein expression of glucocorticoid receptor, caspase-3, and caspase-12. In addition, administration of Xiangshao granules led to the decreased expression of JIK in the PMDD irritability rat model which agreed well with the previous studies. The JNK/p38 mitogen-activated protein kinases (MAPKs) signaling pathway is abnormally activated in the hippocampal brain region of PMDD rats, while treated with Xiangshao granules could increase JIK expression and inhibit the abnormal activation of the JNK/p38 MAPK signaling pathway, effectively reducing the stress damage in the hippocampus. CONCLUSIONS: Xiangshao Granules Reduce the Aggressive Behavior and Hippocampal Injury of Premenstrual Irritability in Rats by Regulating JIK/JNK/p38 Signal Pathway.

Identification reproducible microbiota biomarkers for the diagnosis of cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence in China, which is mainly related to chronic hepatitis B (CHB) and liver cirrhosis (LC) caused by hepatitis B virus (HBV) infection. This study aimed to identify reproducible gut microbial biomarkers across Chinese population for LC and HCC diagnosis. In this study, a group of 21 CHB, 25 LC, 21 HCC and 15 healthy control (HC) were examined, and used as the training data. Four published faecal datasets from different regions of China were collected, totally including 121 CHB, 33 LC, 70 HCC and 96 HC. Beta diversity showed that the distribution of community structure in CHB, LC, HCC was significantly different from HC. Correspondingly, 14 and 10 reproducible differential genera across datasets were identified in LC and HCC, respectively, defined as LC-associated and HCC-associated genera. Two random forest (RF) models based on these reproducible genera distinguished LC or HCC from HC with an area under the curve (AUC) of 0.824 and 0.902 in the training dataset, respectively, and achieved cross-region validations. Moreover, AUCs were greatly improved when clinical factors were added. A reconstructed random forest model on eight genera with significant changes between HCC and non-HCC can accurately distinguished HCC from LC. Conclusively, two RF models based on 14 reproducible LC-associated and 10 reproducible HCC-associated genera were constructed for LC and HCC diagnosis, which is of great significance to assist clinical early diagnosis.

A bibliometric and visual analysis of the use of ustekinumab in Crohn's disease using CiteSpace.

Background: The novel biologic agent ustekinumab (UST), a monoclonal antibody against the p40 subunit of interleukin-12 and interleukin-23, has been applied in the treatment of Crohn's disease (CD). With the development of relevant research, the clinical treatment and favorable prognosis of UST in CD have garnered considerable attention. However, there is a lack of reports that present the current status of UST-related studies in a comprehensive and objective manner. Consequently, this study aims to visually analyze the current status and clinical trends of UST-related research, identify leading researchers, and recognize deficiencies using bibliometrics and knowledge mapping, which might assist in understanding future research priorities in that specific field. Methods: Published articles containing the use of UST in CD were retrieved from the Web of Science core collection database between 2008 and 2022. Then, the bibliometric analysis was performed, and a knowledge map was generated and visualized using the CiteSpace software. Results: A total of 479 articles published between 2008 and 2022 were included in the bibliometric analysis. These publications were authored by 185 scholars from 51 countries or regions, among which the United States (38.3%), Canada (16.9%) and England (10.0%) were predominant in publishing. The keyword analysis indicated that UST has long been a popular biologic agent, and its clinical efficacy, safety, and indication for vulnerable populations in CD are popular research topics. The phrase "fecal calprotectin," a biomarker reflecting the degree of disease activity and monitoring the therapeutic response, began to gain traction in 2020 and has continued to this day. Looking for UST-related biomarkers was gaining clinical attention. Conclusion: The number of clinical studies involving the outcome of UST treatment in CD patients has increased, with the current research focusing on efficacy, safety, indications for vulnerable populations, therapeutic drug monitoring, and biomarkers. As an alternative drug after the failure of traditional immunosuppressive therapies or TNF-α antagonist therapy, UST is an effective and safe therapy in real-world refractory CD patients. UST will remain an active candidate for research in the treatment of CD.

To explore the effect of kaempferol on non-small cell lung cancer based on network pharmacology and molecular docking.

Non-small cell lung cancer (NSCLC) is a common pathological type of lung cancer, which has a serious impact on human life, health, psychology and life. At present, chemotherapy, targeted therapy and other methods commonly used in clinic are prone to drug resistance and toxic side effects. Natural extracts of traditional Chinese medicine (TCM) have attracted wide attention in cancer treatment because of their small toxic and side effects. Kaempferol is a flavonoid from natural plants, which has been proved to have anticancer properties in many cancers such as lung cancer, but the exact molecular mechanism is still unclear. Therefore, on the basis of in vitro experiments, we used network pharmacology and molecular docking methods to study the potential mechanism of kaempferol in the treatment of non-small cell lung cancer. The target of kaempferol was obtained from the public database (PharmMapper, Swiss target prediction), and the target of non-small cell lung cancer was obtained from the disease database (Genecards and TTD). At the same time, we collected gene chips GSE32863 and GSE75037 in conjunction with GEO database to obtain differential genes. By drawing Venn diagram, we get the intersection target of kaempferol and NSCLC. Through enrichment analysis, PI3K/AKT is identified as the possible key signal pathway. PIK3R1, AKT1, EGFR and IGF1R were selected as key targets by topological analysis and molecular docking, and the four key genes were further verified by analyzing the gene and protein expression of key targets. These findings provide a direction for further research of kaempferol in the treatment of NSCLC.