Relationship between lymphocytes and idiopathic macular hole.

BACKGROUND: An idiopathic macular hole (IMH) is a full-thickness anatomic defect extending from the internal limiting membrane to the photoreceptor layer of the macula without any known cause. Recently, clinical laboratory markers of systemic inflammatory status derived from complete blood counts have been evaluated in ocular diseases. This study aimed to explore whether they could predict the development and progression of IMHs. METHODS: A retrospective review of 36 patients with IMH and 36 sex-and-age-matched patients with cataracts was conducted. We collected complete blood counts of all participating individuals and calculated systemic immunoinflammatory indicators. The maximum base diameter of the IMH (BD), minimum diameter of the IMH (MIN), height of the IMH (H), area of the intraretinal cyst (IRC), and curve lengths of the detached photoreceptor arms were measured on optical coherence tomography (OCT) images. We used these values to calculate the macular hole index (MHI), tractional hole index (THI), diameter hole index (DHI), hole form factor (HFF), and macular hole closure index (MHCI). We performed a receiver operating characteristic (ROC) curve analysis of 30 patients with IMH who were followed up 1 month after surgery. RESULTS: Lymphocyte counts were significantly higher in the IMH group. No other significant differences were observed between the IMH and control groups. Lymphocyte counts in the IMH group were significantly negatively correlated with MIN and BD and were significantly positively correlated with MHI, THI, and MHCI. However, lymphocyte counts were not significantly correlated with H, IRC, DHI, and HFF. In the ROC analysis, BD, MIN, MHI, THI, and MHCI were significant predictors of anatomical outcomes. According to the cut-off points of the ROC analysis, lymphocyte counts were compared between the above-cut-off and below-cut-off groups. Lymphocyte counts were significantly higher in the MIN ≤ 499.61 µm, MHI ≥ 0.47, THI ≥ 1.2, and MHCI ≥ 0.81 groups. There were no significant differences between the above-cut-off and below-cut-off BD groups. CONCLUSIONS: Although inflammation may not be an initiating factor, it may be involved in IMH formation. Lymphocytes may play a relatively important role in tissue repair during the developmental and postoperative recovery phases of IMH.

Review of recent advances on health benefits, microbial transformations, and authenticity identification of Citri reticulatae Pericarpium bioactive compounds.

The extensive health-promoting effects of Citri Reticulatae Pericarpium (CRP) have attracted researchers' interest. The difference in storage time, varieties and origin of CRP are closely related to the content of bioactive compounds they contain. The consitituent transformation mediated by environmental microorganisms (bacteria and fungi) and the production of new bioactive components during the storage process may be the main reason for 'the older, the better' of CRP. In addition, the gap in price between different varieties can be as large as 8 times, while the difference due to age can even reach 20 times, making the 'marketing young-CRP as old-CRP and counterfeiting origin' flood the entire market, seriously harming consumers' interests. However, so far, the research on CRP is relatively decentralized. In particular, a summary of the microbial transformation and authenticity identification of CRP has not been reported. Therefore, this review systematically summarized the recent advances on the main bioactive compounds, the major biological activities, the microbial transformation process, the structure, and content changes of the active substances during the transformation process, and authenticity identification of CRP. Furthermore, challenges and perspectives concerning the future research on CRP were proposed.

Detection and identification of imperatorin metabolites in rat, dog, monkey, and human liver microsomes by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry and Compound Discoverer software.

Imperatorin, a furanocoumarin that widely exists in many umbelliferous herbs, has been demonstrated to have a variety of pharmacological effects, including anti-inflammatory, antiosteoporosis, and antitumor activities. The purpose of this study was to investigate the metabolism of imperatorin using liver microsomes. The metabolites were generated by individually incubating imperatorin with rat, dog, monkey, and human liver microsomes. To trap the reactive metabolites during microsomal metabolism, glutathione (GSH) was included in the incubation. A LC technique coupled with benchtop orbitrap MS with full mass/data-dependent tandem mass spectrometry acquisition mode was used to detect and identify the generated metabolites. The possible structures of the metabolites were characterized according to their accurate masses and fragment ions. Under the current conditions, a total of 10 metabolites, including four GSH adducts, were identified. The results indicated that imperatorin underwent extensive metabolic reactions including hydroxylation, oxidation, glucuronidation, and GSH conjugation. This study provides essential data on the metabolism of imperatorin, which will be helpful for us to understand the safety and efficacy of this bioactive compound.

Simultaneous determination of erythrocyte methotrexate polyglutamates by a novel and simple HPLC-MS/MS method with stable isotope-labeled internal standards.

Low-dose methotrexate is the first-line therapy for juvenile idiopathic arthritis. In vivo, methotrexate is converted into a series of methotrexate polyglutamates whose intracellular levels contribute significantly to its efficacy and toxicity. In this study, a novel high-performance liquid chromatography-tandem mass spectrometry method was developed and validated to simultaneously determine erythrocyte methotrexate polyglutamates using stable isotope-labeled internal standards. Erythrocyte samples were precipitated by perchloric acid and then determined on an XBridge BEH C18 column with an XP vanguard precolumn in 12 min. The mobile phase consisted of 10 nM ammonium acetate (pH 10) and methanol under gradient elution. The detection was carried out in multiple reaction monitoring mode via an electrospray ionization source in positive ionization mode. The calibration curve for each metabolite was linear from 2.0 to 500.0 nmol/L (r2  > 0.99). The intraday and interday accuracies were between 93.0 and 107.0%, and the corresponding precisions were between 0.8 and 5.2%. The relative recovery ranged from 82.7 to 105.1%, and the relative matrix effect varied from 96.5 to 104.4%. The erythrocyte metabolites were stable for 30 days at -80°C. This simple and accurate method is applicable to routine monitoring of the concentration of erythrocyte methotrexate polyglutamates in patients to achieve individualized treatment.

Comparison of Pregnancy Outcomes Between Single-Morula Embryo Transfer and Single-Blastocyst Transfer in Fresh IVF/ICSI Cycles.

BACKGROUND This study investigated the effectiveness and feasibility of day 4 (D4) morula embryo transfer (ET) in comparison with day 5 (D5) blastocyst ET, with regards to their clinical data, laboratory test results, and pregnancy outcomes. MATERIAL AND METHODS This retrospective cohort study enrolled 1070 patients, including 178 cases in group D4 and 892 cases in group D5. The endpoint was live birth rate after fresh embryo transfer. Furthermore, the clinical outcomes of D4 embryos with different morphology were compared and assigned to 3 groups: in group 1 (n=66) the embryos were compacted but not expanded, in group 2 (n=102) the embryos were compacted and expanded (early blastocyst), and in group 3 (n=10) the embryos were not compacted. RESULTS Groups D4 and D5 had comparable clinical pregnancy rates (53.37% vs. 59.97%) and live birth rates (43.25% vs 50.89%), and there were no significant differences between the 2 groups. In group 3, there was only 1 clinical pregnancy and no live birth. In comparison between group 1 and group 2, the clinical pregnancy rate of group 2 showed an upward trend (48.48% vs 60.78%), but there was no significant difference. There was also no statistically significant difference in the live birth rate between the 2 groups (42.42% vs 49.01%). CONCLUSIONS Transferring of compacted embryos or early blastocysts can result in high clinical pregnancy rates and live birth rates. In addition to the cleavage and blastocyst ET, morula ET may serve as an alternative option for the clinician.

Kidney podocyte-associated gene polymorphisms affect tacrolimus concentration in pediatric patients with refractory nephrotic syndrome.

Few studies have investigated the correlation between pharmacogenomics and tacrolimus pharmacokinetics in patients with nephrotic syndrome (NS). This study evaluated the influences of genetic polymorphisms of metabolic enzymes, transporters, and podocyte-associated proteins on tacrolimus concentration in Chinese pediatric patients with refractory NS. A total of 167 pediatric patients with refractory NS were included from July 2013 to December 2017. Age of onset was restricted to <14 years of age. Dose-adjusted tacrolimus trough concentration (C0/D) on the third month was calculated, and 20 single-nucleotide polymorphisms in sixteen genes were genotyped. Age was correlated with tacrolimus C0/D (p = 0.006, r = 0.213). Tacrolimus C0/D was higher in CYP3A5 nonexpressers than in CYP3A5 expressers (p = 0.003). ACTN4 rs62121818, MYH9 rs2239781, CYP3A5*3, and age explained 20.5% interindividual variability of tacrolimus concentration in the total cohort. In CYP3A5 nonexpressers, ACTN4 rs62121818 and MYH9 rs2239781 together explained 14.6% variation of tacrolimus C0/D. MYH9 rs2239781, LAMB2 rs62119873 and age together explained 22.3% variability of tacrolimus level in CYP3A5 expressers. CYP3A5*3 was still an important factor affecting tacrolimus concentration in patients with NS. Podocyte-associated gene polymorphisms, especially ACTN4 rs62121818 and MYH9 rs2239781, were the other most important biomarkers for tacrolimus whole blood levels. Genotyping of CYP3A5, ACTN4, and MYH9 polymorphisms may be helpful for better guiding tacrolimus dosing in pediatric patients with refractory NS.

Delayed development influences the outcome of different grades of D5 and D6 blastocysts during freeze-thaw cycle.

To analyze the effects of blastocysts on the 5th day (D5) and 6th day (D6) of frozen-thawed blastocyst transplantation on pregnancy outcome and provide evidence for further improvement of the strategy. This study included transfers from the Reproductive Medicine Center of the Second Affiliated Hospital of Wenzhou Medical University during freeze-thaw cycles from January 2016 to December 2017. They were divided into D5 group (1616 cases) and D6 group (619 cases) according to blastocyst formation and development. Each group was further divided into 5 groups according to the quality of the blastocyst and the number of transplants, making a total of 10 groups. Following the frozen transplantation cycle, the transplanting rate was significantly higher for D5 (41.73%) than for D6 (23.98%) (P < 0.05); the ongoing pregnancy rate (47,40%) was also significantly higher than that of D6 (28.43%) (P < 0.05).In the frozen-thawed blastocyst resuscitation transplantation, compared to D6 blastocysts, D5 blastocysts were more conducive to blastocyst implantation and could be used to achieve better clinical pregnancy outcome. In blastocyst selection, a single D5 excellent blastocyst transplant is preferred. Only at the 6th day of non-excellent D6, 2 blastocysts are recommended for transplantation.

Development and validation of a simple and sensitive high-resolution LC/MS method for determination of PF-04620110 in dog plasma: Application to a pharmacokinetic study.

In this study, a more sensitive and reliable quantitative method based on ultra-high performance liquid chromatography coupled with Q-Exactive-Orbitrap-MS in full-mass scan was developed and validated for the determination of PF-04620110 in dog plasma. After protein precipitation with acetonitrile, the sample separations were carried out on an Acquity BEH C18 column with 1 mm ammonium acetate in water and acetonitrile containing 0.1% acetic acid as mobile phase, at a flow rate of 0.4 mL/min. The assay showed excellent linearity over the concentration range of 1-2000 ng/mL with correlation coefficient >0.9980 (r > 0.9980). The LLOQ was 1 ng/mL. The inter- and intra-day precision (RSD, %) was within 9.69% while the accuracy (RE, %) was in the range of -8.59-11.24%. The extraction recovery was >85.37% and the assay was free of matrix effects. PF-04620110 was demonstrated to be stable under various processing and handing conditions. The validated method was successfully applied to the pharmacokinetic study of PF-04620110 in dogs and the results revealed that PF-04620110 was slowly eliminated from plasma with a clearance of 60.81 ± 7.11 mL/h/kg for intravenous administration and 81.44 ± 25.79 mL/h/kg for oral administration. The oral bioavailability was determined to be 77.89% in dogs.

Light enhanced room temperature resistive NO2 sensor based on a gold-loaded organic-inorganic hybrid perovskite incorporating tin dioxide.

A material is described for sensing NO2 in the gas phase. It has an architecture of type Au/MASnI3/SnO2 (where MA stands for methylammonium cation) and was fabricated by first synthesizing Au/MASnI3 and then crystallizing SnO2 on the surface by calcination. The physical and NO2 sensing properties of the composite were examined at room temperature without and with UV (365 nm) illumination, and the NO2-sensing mechanism was studied. The characterization demonstrated the formation of a p-n heterojunction structure between p-MASnI3 and n-SnO2. The sensor, best operated at a voltage of 1.1 V at room temperature, displays superior NO2 sensing performance. Figures of merit include (a) high response (Rg/Ra = 240 for 5 ppm NO2; where Rg stands for the resistance of a sensor in test gas, and Ra stands for the resistance of a sensor in air), (b) fast recovery (about 12 s), (c) excellent selectivity compared to sensors based on the use of SnO2 or Au/SnO2 only, both at room temperature under UV illumination; (d) a low detection limit (55 ppb), and (e) a linear response between 0.5 and 10 ppm of NO2. The enhanced sensing performance is mainly attributed to the high light absorption capacity of MASnI3, the easy generation and transfer of photo-induced electrons from MASnI3 to the conduction band of SnO2, and the catalytic effect of gold nanoparticles. Graphical abstract Schematic of the energy band diagrams of the gold-functionalized MASnI3/SnO2 system after equilibrium with UV illumination, by which the enhanced sensing performance for NO2 can be explained.

Formation of n-n type heterojunction-based tin organic-inorganic hybrid perovskite composites and their functions in the photocatalytic field.

MASnI3/TiO2 composites (MA represents CH3NH3+) are prepared via a solvothermal method and characterized by various techniques. The results indicate that n-n type heterojunction structures and different ohmic contact interfaces are formed for the composites with different contents of MASnI3 and TiO2 before and after calcination, resulting in different optical and photocatalytic performances. Generally speaking, n-n type heterojunctions play roles in photocatalytic applications through two different mechanisms: the heterojunction mechanism and the Z-type mechanism. The calcined composites with better ohmic contact interfaces mainly follow the Z-type mechanism, which can promote direct radiative recombination of photogenerated carriers. As a result, higher luminous intensities and interface recombination instead of bulk recombination between electrons and holes can be achieved, which improves the photoluminescence and photocatalytic activities of the materials. Moreover, the n-n type heterojunction structure avoids p-type defect states to some degree, which averts the hydrolysis and oxidation of MASnI3 in atmosphere and enhances the long-term stability of the MASnI3/TiO2 composites.

Comparative Effectiveness of Three Ovarian Hyperstimulation Protocol in In Vitro Fertilization (IVF) Cycles for Women with Polycystic Ovary Syndrome.

BACKGROUND The aim of this study was to evaluate the efficacy of specific in vitro fertilization (IVF) protocols for patients with polycystic ovary syndrome (PCOS), and therefore, analyze the first-rank intention IVF protocol. MATERIAL AND METHODS In this study, 408 PCOS patients (464 treatment cycles) were enrolled and assigned to one of 3 groups: group 1 [oral contraceptive long-term regimen group (OC-L protocol group, n=91)], group 2 (GnRH antagonist protocol, n=80), and group 3 [follicular phase long-term regimen group, C1-L protocol group n=293]. The endpoints are the number of eggs, oocyte maturation rate, high-quality embryo rate and clinical pregnancy rate after fresh embryos transfer, the incidence of ovarian hyperstimulation syndrome and abortion rate. RESULTS The number of eggs, oocyte maturation rate, and high-quality embryo rate in the C1-L protocol group were significantly higher than those in the other 2 groups. The fertilization rate and cleavage rate of the 3 groups were not significantly different. After fresh embryo transplantation, the pregnancy rate of C1-L protocol group was significantly higher than that of the other groups. CONCLUSIONS This study showed that the super-long downregulation in follicular phase regimen has advantages of simple treatment process, high oocyte maturation rate, high quality embryo rate, and pregnancy rate. It is a good choice for PCOS patients to promote ovulation during IVF.

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome.

BACKGROUND Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E2) levels, but can experience ovarian hyperstimulation syndrome (OHSS). The aim of this study was to evaluate the effect of oral letrozole, prior to administration of hCG, on the outcome of IVF and development of OHSS. MATERIAL AND METHODS Retrospective clinical review included 181 cases of women with PCOS who underwent IVF cycles with intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF/ICSI-ET). The day before the use of hCG, cases were divided into a letrozole-treated group (N=78) and a non-letrozole group (N=103). An oral dose of 2.5 mg qd of letrozole was given when the peak level of E2 was ≥4000 pg/ml during ovarian stimulation and ceased before the day of egg retrieval. RESULTS The letrozole-treated group had a significant increase in the number of retrieved oocytes, viable embryos, and fresh ET rate (P>0.05); peak levels of E2, and E2 levels on the day of the egg retrieval, were significantly higher, and the fertilization rate was significantly lower (P<0.001). No significant differences were found in the rates of pregnancy, abortion, or ectopic pregnancy between the two groups (P>0.05). The incidence OHSS was lower in the letrozole-treated group, but this difference did not reach statistical significance (P>0.05). CONCLUSIONS Women with PCOS who underwent IVF, oral treatment with letrozole a day prior to treatment with hCG lowered E2 levels, but did not significantly reduce the incidence of OHSS.

The regulation of ovary and conceptus on the uterine natural killer cells during early pregnancy.

Uterine natural killer (uNK) cells are short-lived, terminally differentiated and the most abundant lymphocytes in the uterus which play a crucial role in the spiral arteriole modification and establishment of successful pregnancy. Dysregulation of uNK cells has been linked to gestational implications such as recurrent pregnancy loss, preeclampsia and fetal growth retardation. There is evidence showing that progesterone and estrogen can regulate the recruitment, proliferation, differentiation and function of uNK cells via direct action on intracellular nuclear receptors or through intermediary cells in the uterus during early pregnancy. As the deepening of related research in this field, the role of conceptus in such regulation has received extensive attention, it utilizes endocrine signaling (hCG), juxtacrine signaling (HLA-C, HLA-E, HLA-G) and paracrine signaling (cytokines) to facilitate the activities of uNK cells. In addition, under the influence of ovarian hormones, conceptus can increase expression of PIBF and HLA-G molecules to reduce cytotoxicity of uNK cells and promote angiogenesis. In this review, we aim to concentrate on the novel findings of ovarian hormones in the regulation of uNK cells, emphasize the regulatory role of conceptus on uNK cells and highlight the proposed issues for future research in the field.

Research advances on potential neurotoxicity of quantum dots.

With rapid development of nanotechnology, quantum dots (QDs) as advanced nanotechnology products have been widely used in biological and biomedical studies, including neuroscience, due to their superior optical properties. In recent years, there has been intense concern regarding the toxicity of QDs with a growing number of studies. However, the knowledge of neurotoxic consequences of QDs applied in living organisms is lagging behind their development, while a potential risk of neurotoxicity arises if mass production of QDs leads to increased exposure and distribution in the nervous system. Owing to the quantum size effect of QDs, they are capable of crossing the blood-brain barrier or moving along neural pathways and entering the brain. Nevertheless, the interactions of QDs with cells and tissues in the central nervous system are not well understood. This review highlighted research advances on the neurotoxicity of QDs in the central nervous system, including oxidative stress injury, elevated cytoplasmic Ca(2+) levels and autophagy to damage in vitro neural cells, and impairments of synaptic transmission and plasticity as well as brain functions in tested animals, with the hope of throwing light on future research directions of QD neurotoxicity, which is a demanding topic that requires further exploration.

Hierarchical Porous Reduced Graphene Oxide/Poly(l-lactic acid) Fiber Films: The Influence of Recrystallization on Strength.

Electrospinning technology for fabricating nanofiber films and the Hummer method for synthesizing graphene oxide (GO), along with subsequent reduction, have been significantly advanced, demonstrating immense potential for large-scale industrial applications. Nanofibrous films loaded with reduced graphene oxide (rGO) have been widely explored for their applications in electromagnetic shielding, the biomedical fields, and pollutant adsorption. However, fragile mechanical performance of electrospun fibers with limited surface post-treatment methods has somewhat hindered their further industrial development. In response to this challenge, we propose a dual-regulation strategy involving post-treatment to form porous nanofiber films and the controlled flake size of rGO for surface coating during preparation. This approach aims to achieve poly(l-lactic acid) (PLLA)/rGO electrospun fibrous films with enhanced mechanical properties. It offers a roadmap for the continued application and standardized production of fibrous films loaded with rGO.

Systemic immune-inflammation index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio in patients with type 2 diabetes at different stages of diabetic retinopathy.

AIM: To investigate systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) levels in patients with type 2 diabetes at different stages of diabetic retinopathy (DR). METHODS: This retrospective study included 141 patients with type 2 diabetes mellitus (DM): 45 without diabetic retinopathy (NDR), 47 with non-proliferative diabetic retinopathy (NPDR), and 49 with proliferative diabetic retinopathy (PDR). Complete blood counts were obtained, and NLR, PLR, and SII were calculated. The study analysed the ability of inflammatory markers to predict DR using receiver operating characteristic (ROC) curves. The relationships between DR stages and SII, PLR, and NLP were assessed using multivariate logistic regression. RESULTS: The average NLR, PLR, and SII were higher in the PDR group than in the NPDR group (P=0.011, 0.043, 0.009, respectively); higher in the NPDR group than in the NDR group (P<0.001 for all); and higher in the PDR group than in the NDR group (P<0.001 for all). In the ROC curve analysis, the NLR, PLR, and SII were significant predictors of DR (P<0.001 for all). The highest area under the curve (AUC) was for the PLR (0.929 for PLR, 0.925 for SII, and 0.821 for NLR). Multivariate regression analysis indicated that NLR, PLR, and SII were statistically significantly positive and independent predictors for the DR stages in patients with DM [odds ratio (OR)=1.122, 95% confidence interval (CI): 0.200-2.043, P<0.05; OR=0.038, 95%CI: 0.018-0.058, P<0.05; OR=0.007, 95%CI: 0.001-0.01, P<0.05, respectively). CONCLUSION: The NLR, PLR, and SII may be used as predictors of DR.

Unveiling the role of gut microbiota in curcumin metabolism using antibiotic-treated mice.

Curcumin might exert its therapeutic effects by interacting with gut microbiota. However, the role of gut microbiota in curcumin metabolism in vivo remains poorly understood. To address this, we used antibiotics to deplete gut microbiota and compared curcumin metabolism in control and antibiotic-treated mice. Using Q-TOF and triple quadrupole mass spectrometry, we identified and quantified curcumin metabolites, revealing distinct metabolic pathways in these two mice groups. The novel metabolites, hexahydro-dimethyl-curcumin and hexahydro-didemethyl-curcumin were exclusively derived from gut microbiota. Additionally, gut bacteria deconjugated curcumin metabolites back into their bioactive forms. Moreover, control mice exhibited significantly lower curcumin degradation, suggesting a protective role of gut microbiota against degradation. In conclusion, our results indicated that gut microbiota might enhance the effectiveness of curcumin by deconjugation, production of active metabolites, and protection against degradation in the large intestine. This study enhances our understanding of the interactions between curcumin and gut microbiota.

Facile expression and purification of the antimicrobial peptide histatin 1 with a cleavable self-aggregating tag (cSAT) in Escherichia coli.

Human histatin 1 (Hst1), a member of the histatin family, possesses antimicrobial properties. In this study, we applied a previously developed cleavable self-aggregating tag (cSAT) for the expression and purification of histatin 1 to demonstrate its utility for peptide expression and purification. The tag consists of a self-cleavable intein and a self-assembling peptide ELK16 (I-ELK16). First, an active insoluble aggregate of the recombinant histatin 1-Mxe GyrA intein-ELK16 (Hst1-I-ELK16) fusion protein was produced with a yield of 28.9 µg/mg wet cell pellet. The thiol reagent dithiothreitol (DTT) was then used to induce the intein-mediated cleavage and peptide release into the soluble fraction with a yield of 2.06 µg/mg wet cell pellet and a purity of 70%. The peptide was further purified by high performance liquid chromatography. These results were comparable to the yield and purity achieved when the more conventional glutathione transferase (GST) tag was used. The antimicrobial activities of this recombinant histatin 1 were confirmed against three Candida strains. This cSAT technique offers considerable advantages in terms of its simplicity and speed, eliminating the need for an exogenous protease, and reducing the number of chromatography purification steps. This technique should also be useful for the expression and purification of other AMPs.

Production Technology and Functionality of Bioactive Peptides.

Bioactive peptides are specific protein fragments that prove health-promoting potential for humans. The bioactivities include antimicrobial, antioxidant, anticancer, immunomodulatory activities, etc. Hence, bioactive peptides' production technology and processes have attracted excessive attention, especially concerning peptides' synthesis, separation, identification, and functionality. This review summarizes the relevant investigations from the above four aspects. Among the production technology of bioactive peptides, biosynthesis, chemosynthesis, technology for separation and purification, and the interactions responsible for peptide-based nanostructures are emphasized. Here, the biosynthesis of peptides includes enzymatic hydrolysis, microbial fermentation, and recombinant DNA technology, and chemosynthesis consists of solution-phase peptide synthesis and solid-phase peptide synthesis (SPPS). The commonly used enzymes in enzymatic hydrolysis are investigated, including pepsin, trypsin, and alcalase. The commonly used microorganisms, typical processes, protein sources, and advantages of microbial fermentation are analyzed. Membrane separation (including ultrafiltration and nanofiltration), chromatography technology (including ion-exchange chromatography, gel filtration chromatography, affinity chromatography, and reverse-phase high-performance liquid chromatography (RP-HPLC)), and electrophoresis technology are detailed for the purification technology. Mass spectrometry (MS), its combination with the high-performance separation method, and nuclear magnetic resonance (NMR) are elucidated for the identification technology. The non-covalent interactions responsible for peptide-based nanostructures involve electrostatic force, hydrogen bonds, π-π stacking, hydrophobic interaction, and van der Waals force. Afterward, we detail the peptides' antihypertensive, antithrombotic, anticancer, antimicrobial, antioxidant, and immunomodulatory activities. The activity analysis mainly involves peptides' sources, structural features, mechanisms of action, and influencing factors. Based on the production and functionality elucidation, potential challenges for peptide application in biomedicine are given. The challenge is analyzed from the aspects of purification and identification technologies and influencing factors of peptides' bioactivities. Our work will elaborate on advances in the production technology of peptides and their bioactivities, which could promote and expand their industrial applications.

Dietary tangeretin improved antibiotic-associated diarrhea in mice by enhancing the intestinal barrier function, regulating the gut microbiota, and metabolic homeostasis.

Antibiotic-associated diarrhea is mediated by antibiotic treatment and is usually caused by the disruption of the intestinal barrier, gut microbiota, and metabolic balance. To identify a dietary strategy that can mitigate the side effects of antibiotics, this study investigated the effect of tangeretin on antibiotic-associated diarrhea in C57BL/6 mice. The results revealed that dietary tangeretin significantly ameliorated symptoms of antibiotic-associated diarrhea, as evidenced by the decreased diarrhea status scores, the reduced fecal water content, the decreased caecum/body weight ratio, and the alleviated colonic tissue damage. Dietary tangeretin also exhibited a protective effect on the intestinal barrier function by upregulating the mRNA and protein expression of claudin-1 and ZO-1. Furthermore, analysis of the gut microbiota using 16S rRNA gene sequencing indicated that dietary tangeretin modulated the gut microbiota of mice with antibiotic-associated diarrhea via increasing the gut microbiota diversity and the abundance of beneficial bacteria, e.g., Lactobacillaceae and Ruminococcaceae, and decreasing the abundance of harmful bacteria, e.g., Enterococcus and Terrisporobacter. Additionally, dietary tangeretin restored the levels of short-chain fatty acids and modulated metabolic pathways by enriching purine metabolism, bile acid metabolism, ABC transporters, and choline metabolism in cancer. Collectively, these findings provide a solid scientific basis for the rational use of tangeretin as a preventive and therapeutic agent for antibiotic-associated diarrhea.