Radiation therapy with phenotypic medicine: towards N-of-1 personalization.

In current clinical practice, radiotherapy (RT) is prescribed as a pre-determined total dose divided over daily doses (fractions) given over several weeks. The treatment response is typically assessed months after the end of RT. However, the conventional one-dose-fits-all strategy may not achieve the desired outcome, owing to patient and tumor heterogeneity. Therefore, a treatment strategy that allows for RT dose personalization based on each individual response is preferred. Multiple strategies have been adopted to address this challenge. As an alternative to current known strategies, artificial intelligence (AI)-derived mechanism-independent small data phenotypic medicine (PM) platforms may be utilized for N-of-1 RT personalization. Unlike existing big data approaches, PM does not engage in model refining, training, and validation, and guides treatment by utilizing prospectively collected patient's own small datasets. With PM, clinicians may guide patients' RT dose recommendations using their responses in real-time and potentially avoid over-treatment in good responders and under-treatment in poor responders. In this paper, we discuss the potential of engaging PM to guide clinicians on upfront dose selections and ongoing adaptations during RT, as well as considerations and limitations for implementation. For practicing oncologists, clinical trialists, and researchers, PM can either be implemented as a standalone strategy or in complement with other existing RT personalizations. In addition, PM can either be used for monotherapeutic RT personalization, or in combination with other therapeutics (e.g. chemotherapy, targeted therapy). The potential of N-of-1 RT personalization with drugs will also be presented.

Streamlining complex mandibular fracture treatment: Integration of virtual surgical planning and short-segment drilling guides.

This study aimed to evaluate the feasibility and accuracy of a combined virtual surgical planning (VPS) and short-segment drilling guides (SSDGs) workflow for the treatment of complex mandibular fractures. Consecutive patients with complex mandibular fractures underwent treatment using the VPS and SSDGs workflow from August 2020 to April 2022. Various mandibular landmarks were compared between the preoperative virtual surgical plan and postoperative data, including condylar distance (CoD), mandibular angle width (GoL-GoR), GoMeGo angle (∠GoL-Me-GoR), the difference in mandibular angles between the left and right sides (Δ∠Co-Go-Me), and the difference in length between the left and right mandibular body (ΔGo-Me). Additionally, preoperative preparation time and surgical duration were retrospectively analyzed and compared to conventional surgery. All 14 consecutive patients with complex mandibular fractures achieved successful reduction using the VPS and SSDGs workflow. Three-dimensional comparison revealed a mean deviation distance of 0.91 ± 0.50 mm and a root-mean-square deviation of 1.75 ± 0.47 mm between the preoperative designed mandible model and the postoperative mandible model. The percentage of points with deviation distances less than 2 mm, 1 mm, and 0.5 mm between preoperative and postoperative models were 78.47 ± 8.87 %, 60.02 ± 14.28 %, and 38.64 ± 15.48 %, respectively. There were no significant differences observed in CoD, GoL-GoR, ∠GoL-Me-GoR, Δ∠Co-Go-Me, and ΔGo-Me between preoperative virtual surgical planning and postoperative measurements. Furthermore, no significant differences were found in the injury-to-surgery interval, admission-to-surgery interval, and surgical duration between the workflow and conventional surgery. The combined VPS and SSDGs workflow proved to be an accurate and feasible method for treating complex mandibular fractures. It offers advantages such as minimal preoperative preparation time and the ability to precise transfer screw positions of the pre-bent reconstruction plate during surgery. This approach is particularly suitable for managing complex mandibular fractures.

Impact of the implementation of the Intelligent Antimicrobial System (iAMS) on clinical outcomes among patients with bacteraemia caused by methicillin-resistant Staphylococcus aureus.

OBJECTIVES: This study aimed to investigate the clinical impact of the Intelligent Antimicrobial System (iAMS) on patients with bacteraemia due to methicillin-resistant (MRSA) and methicillin-susceptible Staphylococcus aureus (MSSA). METHODS: A total of 1008 patients with suspected SA infection were enrolled before and after the implementation of iAMS. Among them, 252 with bacteraemia caused by SA, including 118 in the iAMS and 134 in the non-iAMS groups, were evaluated. RESULTS: The iAMS group exhibited a 5.2% (from 55.2% to 50.0%; P = 0.96) increase in the 1-year survival rate. For patients with MRSA and MSSA compared to the non-iAMS group, the 1-year survival rate increased by 17.6% (from 70.9% to 53.3%; P = 0.41) and 7.0% (from 52.3% to 45.3%; P = 0.57), respectively, both surpassing the rate of the non-iAMS group. The iAMS intervention resulted in a higher long-term survival rate (from 70.9% to 52.3%; P = 0.984) for MRSA patients than for MSSA patients. MRSA patients experienced a reduced length of hospital stay (from 23.3% to 35.6%; P = 0.038), and the 45-day discharge rate increased by 20.4% (P = 0.064). Furthermore, the intervention resulted in a significant 97.3% relative decrease in near miss medication incidents reported by pharmacists (P = 0.013). CONCLUSIONS: Implementation of iAMS platform improved long-term survival rates, discharge rates, hospitalization days, and medical cost (although no significant differences were observed) among patients with MRSA bacteraemia. Additionally, it demonstrated significant benefits in ensuring drug safety.

Structure-activity relationship of Caulerpa lentillifera polysaccharide in inhibiting lipid digestion.

Caulerpa lentillifera polysaccharide (CLP) has been characterized as a sulfated polysaccharide which can effectively inhibit lipid digestion. However, little information was known regarding its inhibitory mechanisms. In the present study, desulfation and degradation were conducted to prepare the derivatives of CLP, and a series of chemical and spectroscopic methods were used to elucidate the structure-activity relationship of CLP on the inhibitory effect of lipid digestion. Results revealed that CLP possessed excellent binding capacities for sodium cholate, sodium glycocholate, and sodium taurocholate. In addition, CLP can effectively inhibit lipase activity by quenching the fluorescence intensity, changing the secondary structure, and decreasing the UV-Vis absorbance. Of note, sulfate groups in CLP took a vital role in inhibiting lipase activity, while the molecular weight of CLP showed a positive correlation with the binding activities of bile acids. Furthermore, adding CLP into the whey protein isolate (WPI) emulsion system also impeded lipid digestion, indicating that CLP can be a potential reduced-fat nutraceutical used in food emulsion systems.

Intracranial Germ Cell Tumors.

Intracranial germ cell tumors are rare tumors occurring in adolescents and young adults, which include germinomas and non-germinomatous type germ cell tumors (NGGCT). In the past few decades, cooperative trial groups in Europe and North America have developed successful strategies to improve survival outcomes and decrease treatment-related toxicities. New approaches to establishing diagnosis have deferred the need for radical surgery. The 5-year event-free survival (EFS) is above 90% and even patients who present with metastatic germinoma can still be cured with chemotherapy and craniospinal irradiation. The combination of surgery, chemotherapy, and radiation therapy is tailored to patients based on grouping and staging. For NGGCT, neoadjuvant chemotherapy followed by delayed surgery for residual disease and radiotherapy can yield a 5-year EFS of 70%. Further strategies should focus on reducing long-term complications while preserving high cure rates.

The Impact of Exercise Training on Physical Activity among Elderly Women in the Community: A Pilot Study.

According to a survey conducted by the Taiwanese government, the elderly spend most of their time watching TV for their daily leisure activities, and most do not pant or sweat during exercise. Relevant studies have shown that physical activity has benefits and importance for the physical functions of the elderly. The objective of this study was to investigate the effects of exercise training on the functional fitness of elderly females in the community. The women subjects were from the community of Kaohsiung City, Taiwan. In total, 34 females were randomly divided into an intervention group and a control group. The ages of the subjects ranged from 65 to 80 years old, with an average age of 75.13. The experimental group continued their physical activity intervention for 20 weeks. The control group had no training plan. The results of the study showed that after 20 weeks of intervention, participants in the intervention group experienced improvements in back grasping, right-hand grip strength, sitting to standing, right hip flexion, right knee extension, right ankle dorsiflexion, right sitting forward extension balance, and sitting back around objects. Six-minute walking distances also showed a significant difference in all cases. The results demonstrated that the 20-week physical activity program intervention used in this study can assist in improving back grasping, right-hand grip strength, sitting to standing, right-hand sitting posture, forward balance, sitting back around objects, and six-minute walking distance among older women in the community. In summary, we recommend a moderate-intensity physical activity exercise program for older women in the community.

Efficacy of Warfarin Therapy Guided by Pharmacogenetics: A Real-world Investigation Among Han Taiwanese.

PURPOSE: The anticoagulation activity of warfarin in populations with CYP2C9, VKORC1, and CYP4F2 variants differs between individuals and is correlated with poor international normalized ratio (INR) control. Pharmacogenetics-guided warfarin dosing has been successfully developed for patients with genetic variations in recent years. However, few real-world data have been used to investigate the INR and warfarin dosage and the time to target INR. This study examined the largest collection of genetic and clinical real-world data related to warfarin to provide further evidence supporting the benefits of pharmacogenetics in clinical outcomes. METHODS: We retrieved a total of 69,610 INR-warfarin records after the index date from 2,613 patients in the China Medical University Hospital database between January 2003 and December 2019. Each INR reading was obtained from the latest laboratory data after the hospital visit date. Patients with a history of malignant neoplasms or pregnancy before the index date were excluded, as were patients without data on INR measurements after the fifth day of prescription, genetic information, or gender variables. The primary outcomes were the INR and warfarin dosage during days 7, 14, 28, 56, and 84 after prescription. The secondary outcome was the time required to reach the INR ranges of 1.5 to 3.0 and >4.0. FINDINGS: A total of 59,643 INR-warfarin records from 2188 patients were retrieved. The average INR was higher for homozygous carriers of the minor allele at CYP2C9 and VKORC1 during the first 7 days (1.83 [1.03] [CYP2C9*1] and 2.46 [1.44] [CYP2C9*3], P < 0.001; 1.39 [0.36] [rs9923231 G/G], 1.55 [0.79] [rs9923231 G/A], and 1.96 [1.13] [rs9923231 A/A], P < 0.001) than for the wild-type allele. These patients with variants required lower warfarin doses than those with the wild-type allele during the first 28 days. CYP4F2 variant patients seemed to require higher doses of warfarin than those in the wild-type group; however, no significant difference in the average INR was observed (1.95 [1.14] [homozygous V433 carriers], 1.78 [0.98] [heterozygous V433M carriers], and 1.66 [0.91] [homozygous M433 carriers], P = 0.016). IMPLICATIONS: Our study indicates that genetic variants in the Han population may enhance warfarin responsiveness, which holds clinical relevance. An increased warfarin dosage was not linked to a shorter time to therapeutic INR between CYP4F2 variant patients and those with a wild-type allele. Assessing CYP2C9 and VKORC1 genetic polymorphisms before initiating warfarin treatment in real-world practice is essential for potentially vulnerable patients and is likely to optimize therapeutic dosing.

Molecular characterization of TNF-ß and IFN-γ in yellowfin seabream (Acanthopagrus latus, Hottuyn, 1782) and their immune responses to density stress during transport.

The inflammatory cytokines TNF-ß and IFN-γ are important mediators of the vertebrate inflammatory response and coordinators of the immune system in regard to NF-κB signalling pathways. In this study, the TNF-ß and IFN-γ genes of yellowfin seabream, Acanthopagrus latus were identified, and the multiple sequence alignments, evolutionary relationships and gene expressions of the two genes were also determined. AlTNF-ß contained a 762 bp open reading frame (ORF) encoding 253 amino acids, while AlIFN-γ contained a 582 bp ORF encoding 193 amino acids. An amino-acid sequence alignment analysis showed that these proteins have highly conserved transmembrane structural domains among teleosts. Moreover, AlTNF-ß has a close affinity with TNF-ß of yellowfin seabream while AlIFN-γ has a high evolutionary correlation with A. regius and Sparus aurata. In addition, the mRNAs of AlTNF-ß and AlIFN-γ are widely expressed in various tissues. AlTNF-ß is highly expressed in gill and intestinal tissues, and the mRNA levels of AlIFN-γ are higher in spleen, skin, and gill tissues than in other tissues. Under transportation density stress, the mRNA level of AlTNF-ß was significantly elevated in the intestine of the high-density group, while AlTNF-ß transcription in the gills did not vary significantly among the density groups. Furthermore, AlIFN-γ expression was increased in liver, intestinal, and gill tissues under high transportation density. The results of this study show that TNF-ß and IFN-γ expression in yellowfin seabream is greatly affected by density stress. The density of 125 per bag for 4-5 cm fry or 1200 per bag for 1-2 cm fry is most suitable for the transportation of live fish. These results might provide a reference for further studies on the immunomodulatory response process and auxiliary function of immune stress of TNF and IFN genes in fish under density stress.

"One-pot" preparation and adsorption performance of chitosan-based La3+/Y3+ dual-ion-imprinted thermosensitive hydrogel.

Temperature-sensitive materials are increasingly of deep interest to researchers. Ion imprinting technology is widely used in the field of metal recovery. In order to solve the problem of rare earth metal recovery, we designed a temperature-sensitive dual-imprinted hydrogel adsorption product (CDIH) with chitosan as the matrix, N-isopropylacrylamide as a thermally responsive monomer, and La3+ and Y3+ as the co-templates. The reversible thermal sensitivity and ion-imprinted structure were determined by differential scanning calorimetry, Fourier transform infrared spectrometer, Raman spectra, Thermogravimetric analysis, X-ray photoelectron spectroscopy, Scanning electron microscopy and X-ray energy spectroscopy various characterizations and analyses. The simultaneous adsorption amount of CDIH for La3+ and Y3+ was 87.04 mg/g and 90.70 mg/g, respectively. The quasi-secondary kinetic model and Freundlich isotherms model well described the adsorption mechanism of CDIH. It's worthy to mention that CDIH could be well regenerated through washing with deionized water at 20 °C, with a desorption rate of 95.29 % for La3+ and 96.03 % for Y3+. And after 10 cycles of reuse, 70 % of the adsorption amount could be maintained, revealing excellent reusability. Furthermore, CDIH expressed better adsorption selectivity to La3+ and Y3+ than its non-imprinted counterparts in a solution containing six metal ions.

Sound Quality Performance of Orthogonal Antisymmetric Composite Laminates Embedded with SMA Wires.

Orthogonal antisymmetric composite laminates embedded with shape memory alloys (SMAs) wires have the potential to improve the sound quality of vibro-acoustics by taking advantage of the special superelasticity, temperature phase transition, and pre-strain characteristics of SMAs. In this research, space discretion and mode decoupling were employed to establish a vibro-acoustic sound quality model of SMA composite laminates. The association between the structural material parameters of SMA composite laminates and the sound quality index is then approached through methodologies. Numerical analysis was implemented to discuss the effects of SMA tensile pre-strain, SMA volume fraction, and the ratio of resin-to-graphite in the matrix on the vibro-acoustic sound quality of SMA composite laminates within a temperature environment. Subsequently, the sound quality test for SMA composite laminates is thus completed. The theoretically predicted value appears to agree well with the experimental outcomes, which validates the accuracy and applicability of the dynamic modeling theory and method for the sound quality of SMA composite laminates. The results indicate that attempting to alter the SMA tensile pre-strain, SMA volume fraction, and matrix material ratio can be used to modify loudness, sharpness, and roughness, which provides new ideas and a theoretical foundation for the design of composite laminates with decent sound quality.

Combining mechanisms of black carbon and magnetic minerals in power plant fly ash.

Black carbon (BC), one of the pollutants emitted from fossil fuel combustion, is closely associated with minerals and other hazardous substances. To date, little is known about the mechanisms between BC and magnetic minerals. Accordingly, further investigating the association between magnetic minerals and BC is necessary. In this work, the extraction of BC from fly ash and the magnetic fraction from BC was achieved by flotation and magnetic separation, respectively. The morphology, mineralogical composition, and magnetic properties of BC and magnetic fraction were characterized by FTIR, XRD, SEM-EDS, and vibrating sample magnetometer (VSM). The results show that BC and magnetic minerals have similar mineral compositions, rich in quartz, mullite, magnetite, and hematite. The magnetic minerals have prominent spherical characteristics and are distributed on the surface and inside the pores of BC with irregular honeycomb features. The VSM and XRD analyses show that Fe3O4 is the primary magnetic material. Moreover, large amounts of C, O, and Fe around and on the surface of magnetic spheres were detected by EDS, indicating that the spherical particles may be the structure of BC-coated Fe3O4. Pyrolysis experiments showed that the yield of the magnetic fraction in the pyrolysis product reached 60 %, far exceeding the theoretical yield of 12 % based on 5 % of doped Fe. This further proves that Fe3O4 was combined with a large number of organics during its formation, which may be due to coating and chemical adsorption. Quantum chemical calculations also confirmed this chemical adsorption between Fe3O4 with BC based on density flooding theory, in which adsorption energies ranged from -213.374 KJ/mol to -827.741 KJ/mol.

Characterization and Gel Properties of Low-Molecular-Weight Carrageenans Prepared by Photocatalytic Degradation.

Low-molecular-weight carrageenan has attracted great interest because it shows advantages in solubility, absorption efficiency, and bioavailability compared to original carrageenan. However more environment-friendly and efficient methods to prepare low-molecular-weight carrageenan are still in great need. In the present study, a photocatalytic degradation method with only TiO2 has been developed and it could decrease the average molecular weight of κ-carrageenan to 4 kDa within 6 h. The comparison of the chemical compositions of the degradation products with those of carrageenan by FT-IR, NMR, etc., indicates no obvious removement of sulfate group, which is essential for bioactivities. Then 20 carrageenan oligosaccharides in the degradation products were identified by HPLC-MSn, and 75% of them possessed AnGal or its decarbonylated derivative at their reducing end, indicating that photocatalysis is preferential to break the glycosidic bond of AnGal. Moreover, the analysis results rheology and Cryo-SEM demonstrated that the gel property decreased gradually. Therefore, the present study demonstrated that the photocatalytic method with TiO2 as the only catalyst has the potential to prepare low-molecular-weight carrageenan with high sulfation degree and low viscosity, and it also proposed the degradation rules after characterizing the degradation products. Thus, the present study provides an effective green method for the degradation of carrageenan.

H2O2-TiO2 photocatalytic degradation of chondroitin sulfate and in vivo absorption and excertion of its product.

Chondroitin sulfate (CS) is widely known for its various biological activities which are closely related to the sulfate substitution and the molecular weight. Effective degradation methods without striping sulfate groups are in a need. In the present study, a photocatalytic degradation method using H2O2 and TiO2 has been developed and it could decrease the average molecular weight of CS into 5 kDa within 6 h. The chemical composition of CS before and after degradation were compared by FT-IR, NMR, etc., and no removement of sulfate group was observed. Then the identification of the oligosaccharides in the degradation product by mass spectroscopy revealed that glucuronic acid or its derivative, arabinuronic acid, was at most of the reducing ends, and the depolymerization mechanism was proposed. Furthermore, the absorption of CS in rats was enhanced by the degradation while the excertion profile of the degradation product was similar to that of CS.

Pb2+-imprinted thermosensitive antibacterial adsorbent derived from sodium alginate and PNIPAM for Pb2+ recovery.

Two sodium alginate-based Pb2+-imprinted thermosensitive hydrogels (SPIT (without ɛ-PL) and SPPIT (with ɛ-PL)) were synthesized, with sodium alginate and ɛ-polylysine (ɛ-PL) as the matrix, N-isopropylacrylamide as the monomer. Characterization with differential scanning calorimeter, Fourier transform infrared spectroscopy, thermogravimetric analyzer, scanning electron microscopy, X-ray photoelectron spectroscopy, and Raman spectroscopy confirmed the aimed structure of the hydrogels. The adsorption capacity of SPIT and SPPIT for Pb2+ was 98.64 mg/g and 153.49 mg/g, respectively. Washing the Pb2+-loaded adsorbent with 10 °C deionized water, SPIT and SPPIT achieved a desorption efficiency of 94.59 % and 97.51 %, respectively. After 10 cycles of adsorption-desorption process, the adsorption capacity and desorption efficiency remained at about 80-88 % of the original ones, expressing excellent reusability. In a mixture containing eight metal ions (Pb2+, Cu2+, Mg2+, Ca2+, Cd2+, Na+, K+, Fe3+), the adsorption capacity of SPIT to Pb2+ was 92.49 mg/g, and that of SPPIT was 102.49 mg/g, much higher than that to the other ions (1.50-11.38 mg/g on SPIT, 9.48-27.45 mg/g on SPPIT), showing excellent adsorption selectivity. The introduction of ɛ-PL enhanced the adsorption capacity, antibacterial ability and stability of the hydrogel, ensuring better application potential in real wastewater.

Supplement of Caulerpa lentillifera polysaccharide by pre-prandial gavage and free feeding demonstrates differences to prevent obesity and gut microbiota disturbance in mice.

BACKGROUND: Caulerpa lentillifera has received extensive attention regarding expansion of its farming and increasing consumption. In our previous study, the structure of C. lentillifera polysaccharide (CLP) was elucidated. However, little information is available about its health effects. In this study, the anti-obesity effect of CLP was investigated by using a high-fat diet-induced obese mice model with two different supplementation methods. RESULTS: In vitro simulated digestion results showed that CLP significantly decreased the lipid digestibility and induced the lipid droplets aggregation in the intestinal stage to inhibit the absorption of lipids. As revealed by 16S ribosomal RNA sequencing and non-targeted metabolomics, supplement of CLP by both pre-prandial gavage and free feeding patterns effectively prevented mice obesity via ameliorating intestinal flora disturbance and regulating bile acids circulation metabolism. Of note was that CLP administration had no effect on short-chain fatty acids production, suggesting the anti-obesity effect was uncorrelated with their production. Moreover, pre-prandial administration of CLP had a better anti-obesity effect in lowering body weight and serum lipid levels, but the free feeding resulted in a higher α-diversity of gut microbiota. CONCLUSION: The findings of this study indicate that CLP could be a potential anti-obesity nutraceutical and that pre-prandial supplement of CLP may be a better intake method to exhibit its hypolipidemic effect. © 2022 Society of Chemical Industry.

Forensic Validation and Application Evaluation of IDentifier DNA Typing Kit (Yan-Huang34).

OBJECTIVES: To investigate the technical performance of IDentifier DNA typing kit (YanHuang34) and evaluate its forensic application value. METHODS: Following the Criterion of Forensic Science Human Fluorescence STR Multiplex Amplification Reagent (GB/T 37226-2018), IDentifier DNA typing kit (YanHuang34) was verified in 11 aspects of species specificity, veracity, sensibility, adaptability, inhibitor tolerance, consistency, balance, reaction condition verification, mixed samples, stability and inter batch consistency. The system efficiency of IDentifier DNA typing kit (YanHuang34) was compared with the PowerPlex® Fusion 6C System, VersaPlex® 27PY System and VeriFilerTM Plus PCR Amplification Kit. The IDentifier DNA typing kit (YanHuang34) was used to detect the swabs of biological samples in daily cases and the STR performances were observed. RESULTS: IDentifier DNA typing kit (YanHuang34) had good species specificity, veracity, adaptability, inhibitor tolerance and balance. The sensibility was up to 0.062 5 ng. It was able to detect different types of samples, degraded samples and inhibitor mixed samples. Complete DNA typing could be obtained for samples with the mixture ratio less than 4∶1. The system efficiency of IDentifier DNA typing kit (YanHuang34) was very high, with TDP up to 1-1.08×10-37, CPEtrio and CPEduo up to 1-5.47×10-14 and 1-6.43×10-9, respectively. For the touched biological samples in actual cases, the effective detection rate was 21.05%. The system efficiency of kinship, single parent and full sibling identifications was effectively improved. CONCLUSIONS: The IDentifier DNA typing kit (YanHuang34) is adaptive to the GB/T 37226-2018 requirements. It can be used for individual identification and paternity identification, and is suitable for application in the field of forensic science.

Dietary fibers obtained from Caulerpa lentillifera prevent high-fat diet-induced obesity in mice by regulating the gut microbiota and metabolite profiles.

Due to its expanded farming and growing consumption, Caulerpa lentillifera has received extensive attention. In the present study, the physicochemical properties of insoluble dietary fibers from C. lentillifera (CL-IDFs) were evaluated in vitro, and 16S rRNA sequencing analysis as well as non-targeted metabolomics were performed to investigate the hypolipidemic effects of CL-IDFs and their combined supplementation (CL-TDFs, composed of CL-IDFs and soluble polysaccharides of C. lentillifera) in vivo. The results show that CL-IDFs exhibited superior physicochemical capacities on the binding of water, oil, and glucose. In addition, CL-IDF and CL-TDF administration could regulate the gut microbiota, increase acetic and propionic acid levels, and restore the metabolic disorders of amino, fatty, and bile acids in obese mice. Notably, considering the processing cost of C. lentillifera and the equal anti-obesity effects of CL-IDFs and CL-TDFs, fresh whole-food supplementation of C. lentillifera may be a cost-effective way to prevent obesity.

Vitamin B6 Metabolic Pathway is Involved in the Pathogenesis of Liver Diseases via Multi-Omics Analysis.

Purpose: To clarify the underlying regulatory mechanisms of progression from liver cirrhosis to hepatocellular carcinoma (HCC), we analyzed the microbiomics, metabolomics, and proteomics in plasma and tissues from patients with HCC or decompensated liver cirrhosis (DC). Patients and Methods: Tissues and plasma from 44 HCC patients and 28 patients with DC were collected for metabolomic analysis. 16S rRNA sequencing was performed in nine HCC tissues (HCCT), four distal noncancerous tissues (HCCN), and 11 DC tissues (DCT). Five HCC tissues had liver cirrhosis (HCCT-LC). Five hepatocellular carcinoma tissues without liver cirrhosis (HCCT-NLC) and five DCT were selected for proteomic sequencing. After combining proteomic and metabolomic analysis, we constructed a mouse model of chronic liver injury using carbon tetrachloride (CCl4) and treated them with vitamin B6 (VB6). Results: 16s rRNA sequence results showed that HCC tissues had higher alpha diversity. The highest LDA scores were detected for Elizabethkingia in HCCT, Subsaxibacter in DCT, and Stenotrophomon in HCCN. Metabolomics results demonstrated some metabolites, including capric acid, L-threonate, choline, alpha-D-Glucose, D-ribose, betaine, 2E-eicosenoic acid, linoleic acid, L-palmitoylcarnitine, taurodeoxycholic acid, L-pyroglutamic acid, androsterone sulfate, and phthalic acid mono-2-ethylhexyl ester (MEHP), had better diagnostic efficacy than AFP (AUC: 0.852; 95% CI: 0.749, 0.954). In a combined analysis of metabolomics and proteomics, we found that HCCT-LC had more obvious disorders of VB6 metabolism and pentose and glucuronate interconversions than DCT, and kynurenine metabolism disorder was more significant in HCCT-LC than in HCCT-NLC. In the CCl4-induced chronic liver injury model, after VB6 supplementation, inflammatory cell infiltration, hepatocyte edema, and degeneration were significantly improved. Conclusion: We found significant differences in the flora distribution between HCCT and DC; MEHP was a new diagnostic biomarker of HCC, and VB6 ameliorated the inflammatory cell infiltration, hepatocyte edema, and degeneration in chronic liver injury.

The effect of Lactobacillus rhamnosus B10 on alcoholic liver injury and intestinal microbiota in alcohol-induced mice model.

Lactobacillus rhamnosus B10 (L. rhamnosus B10) isolated from the baby feces was given to an alcohol mice model, aiming to investigate the effects of L. rhamnosus B10 on alcoholic liver injury by regulating intestinal microbiota. C57BL/6N mice were fed with liquid diet Lieber-DeCarli with or without 5% (v/v) ethanol for 8 weeks, and treated with L. rhamnosus B10 at the last 2 weeks. The results showed that L. rhamnosus B10 decreased the serum total cholesterol (1.48 mmol/L), triglycerides (0.97 mmol/L), alanine aminotransferase (26.4 U/L), aspartate aminotransferase (14.2 U/L), lipopolysaccharide (0.23 EU/mL), and tumor necrosis factor-α (138 pg/mL). In addition, L. rhamnosus B10 also reduced the liver triglycerides (1.02 mmol/g prot), alanine aminotransferase (17.8 mmol/g prot) and aspartate aminotransferase (12.5 mmol/g prot) in alcohol mice, thereby ameliorating alcohol-induced liver injury. The changes of intestinal microbiota composition on class, family and genus level in cecum were analyzed. The intestinal symbiotic abundance of Firmicutes was elevated while gram-negative bacteria Proteobacteria and Deferribacteres was decreased in alcohol mice treated with L. rhamnosus B10 for 2 weeks. In summary, this study provided evidence for the therapeutic effects of probiotics on alcoholic liver injury by regulating intestinal flora.