Selection of Fermentation Supernatant from Probiotic Strains Exhibiting Intestinal Epithelial Barrier Protective Ability and Evaluation of Their Effects on Colitis Mouse and Weaned Piglet Models.

The intestinal epithelial barrier can prevent the invasion of pathogenic microorganisms and food antigens to maintain a consistent intestinal homeostasis. However, an imbalance in this barrier can result in various diseases, such as inflammatory bowel disease, malnutrition, and metabolic disease. Thus, the aim of this study was to select probiotic strains with epithelial barrier-enhancing ability in cell-based model and further investigate them for their improving effects on colitis mouse and weaned piglet models. The results showed that selected specific cell-free fermentation supernatants (CFSs) from Ligilactobacillus salivarius P1, Lactobacillus gasseri P12, and Limosilactobacillus reuteri G7 promoted intestinal epithelial cell growth and proliferation, strengthening the intestinal barrier in an intestinal epithelial cell line Caco-2 model. Further, the administration of CFSs of L. salivarius P1, L. gasseri P12, and L. reuteri G7 were found to ameliorate DSS-induced colitis in mice. Additionally, spray-dried powders of CFS from the three strains were examined in a weaned piglet model, only CFS powder of L. reuteri G7 could ameliorate the feed/gain ratio and serum levels of D-lactate and endotoxin. In conclusion, a new potential probiotic strain, L. reuteri G7, was selected and showed ameliorating effects in both colitis mouse and weaned piglet models.

Discovery of a New Compound, Erinacerin W, from the Mycelia of Hericium erinaceus, with Immunomodulatory and Neuroprotective Effects.

One new compound with an isoindolinone skeleton, along with erinacines A, C, and S, was isolated from the mycelia of Hericium erinaceus, an edible fungus with a long history of use in traditional Chinese medicine. Based on analysis of MS and NMR spectral data, the structure of the compound was identified as (2E,6E)-8-(2-(1-carboxy-3-methylbutyl)-4,6-dihydroxy-1-oxoisoindolin-5-yl)-2,6-dimethylocta-2,6-dienoic acid. In light of this discovery, we have given this compound the name erinacerin W. Using a co-culture in vitro LPS-activated BV2 microglia-induced SH-SY5Y neuroinflammation model, the results showed that erinacerin W demonstrated protection against the LPS-activated BV-2 cell-induced overexpression of IL-6, IL-1ß, and TNF-α on SH-SY5Y cells. This finding may provide potential therapeutic approaches for central nervous disorders.

Recent trends in lactic acid-producing microorganisms through microbial fermentation for the synthesis of polylactic acid.

Polylactic acid (PLA) is a range of unique bioplastics that are bio-based and biodegradable. PLA is currently driving market expansion for lactic acid (LA) due to its high demand as a building block in production. One of the most practical and environmentally benign techniques for synthesising PLA is through enzymatic polymerisation of microbial LA monomers. However, microbial LA fermentation does have some limitations. Firstly, it requires the use of a nutritionally rich medium. Secondly, LA production can be disrupted by bacteriophage infection or other microorganisms. Lastly, the yield can be low due to the formation of by-products through heterofermentative pathway. Considering the potential use of PLA as a replacement for conventional petrochemical-based polymers in industrial applications, researchers are focused on exploring the diversity of LA-producing microorganisms from various niches. Their goal is to study the functional properties of these microorganisms and their ability to produce industrially valuable metabolites. This review highlights the advantages and disadvantages of lactic acid-producing microorganisms used in microbial fermentation for PLA synthesis.

Associations of VEGF Polymorphisms With Retinopathy of Prematurity.

Purpose: This study investigated the associations between vascular endothelial growth factor (VEGF) polymorphisms and retinopathy of prematurity (ROP) risk. Methods: Infants born prematurely at any time from 2009 to 2018 were included. Five single-nucleotide polymorphisms (SNPs) of VEGF were analyzed using real-time PCR in all infants. Multivariate logistic regression was applied to model the associations between VEGF polymorphisms and ROP susceptibility, severity, and premature clinicopathologic characteristics. Results: A total of 334 patients were included and categorized into three groups: those without ROP, those with mild ROP (i.e., ROP not requiring treatment), and those with severe ROP (i.e., ROP for whom treatment was indicated). Among the female patients with ROP, those with VEGF rs3025035 CT (3.231-fold; 95% confidence interval [CI], 1.238-8.431) and a combination of CT and TT genotypes (2.643-fold; 95% CI, 1.056-6.619) exhibited significantly higher risks of severe ROP compared with those with wild-type genotypes. Female ROP infants with VEGF rs3025010 C (TC + CC) alleles had a lower risk of ROP stage ≥3 (odds ratio [OR] = 0.406; 95% CI, 0.165-0.999) than those with TT homozygotes. ROP patients with the VEGF rs10434 A allele (GA + AA) exhibited higher risks of necrotizing enterocolitis (OR = 2.750; 95% CI, 1.119-6.759) and lower risk of bronchopulmonary dysplasia (OR = 0.390; 95% CI, 0.173-0.877) than those with GG homozygotes did. Conclusions: VEGF polymorphisms affect ROP risks differently in male and female infants. In female infants, VEGF rs3025035 with T alleles may predict ROP severity, and VEGF rs3025010 with C alleles may protect against severe ROP.

Intraluminal Therapy for Helicobacter pylori Infection-Comparison of Medicament Containing Tetracycline, Metronidazole, and Bismuth versus Amoxicillin, Metronidazole, and Clarithromycin: A Randomized Controlled Study.

Helicobacter pylori (H. pylori) can be eradicated immediately via local application of single-dose medicament on endoscopic examination. In our previous report, "the eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95) using medicament containing amoxicillin, metronidazole, and clarithromycin". We aimed to evaluate the efficacy and adverse events of medicament containing tetracycline, metronidazole, and bismuth and to improve the efficacy of stomach acid control before ILTHPI. After usage of dexlansoprazole (60 mg b.i.d.) or vonoprazan (20 mg q.d.) for 3 days before ILTHPI, 103 of 104 (99.1%) symptomatic H. pylori-infected treatment-naïve patients achieved levels of stomach pH ≥ 6. Patients were randomized to receive ILTHPI with medicaments containing tetracycline, metronidazole, and bismuth (Group A, n = 52) or amoxicillin, metronidazole, and clarithromycin (Group B, n = 52). The eradication rate of ILTHPI was similar between Group A (76.5%; 39/51) and Group B (84.6%, 44/52) (p = 0.427) and the adverse event was mild diarrhea (2.9%; 3/104). The eradication rate significantly increased from 53.7% (51/95) to 84.6% (44/52) after acid control (p = 0.0004) for Group B patients. The overall eradication rates of successful ILTHPI plus 7-day non-bismuth (Group A) or 7-day bismuth (Group B) oral quadruple therapy for ILTHPI failure patients were both excellent (96.1% for Group A and 98.1% for Group B).

Freshwater transfer affected intestinal microbiota with correlation to cytokine gene expression in Asian sea bass.

As a catadromous fish, Asian sea bass (Lates calcarifer) juveniles migrate from seawater (SW) to freshwater (FW) for growth and development. During migration, they undergo physiological changes to acclimate to environmental salinity. Thus, it is crucial to understand how SW-to-FW migration affects the gut microbiota of catadromous fish. To the best of our knowledge, no study has revealed the effects of transfer to hypotonic environments on a catadromous fish microbiota. In this study, we aimed to determine the effects of FW transfer on the microbiota and cytokine gene expression in the intestines of juvenile catadromous Asian sea bass. The relationship between the water and the gut microbiota of this euryhaline species was also examined. We found that FW transfer affected both mucosa- and digesta-associated microbiota of Asian sea bass. Plesiomonas and Cetobacterium were dominant in both the mucosa- and digesta-associated microbiota of FW-acclimated sea bass. The pathogenic genera Vibrio, Staphylococcus, and Acinetobacter were dominant in the SW group. Although dominant fish microbes were present in the water, fish had their own unique microbes. Vitamin B6 metabolism was highly expressed in the FW fish microbiota, whereas arginine, proline, and lipid metabolism were highly expressed in the SW fish microbiota. Additionally, the correlation between cytokine gene expression and microbiota was found to be affected by FW transfer. Taken together, our results demonstrated that FW transfer altered the composition and functions of mucosa- and digesta-associated microbiota of catadromous Asian sea bass intestines, which correlated with cytokine gene expression.

Systemic Cytokines in Retinopathy of Prematurity.

Retinopathy of prematurity (ROP), a vasoproliferative vitreoretinal disorder, is the leading cause of childhood blindness worldwide. Although angiogenic pathways have been the main focus, cytokine-mediated inflammation is also involved in ROP etiology. Herein, we illustrate the characteristics and actions of all cytokines involved in ROP pathogenesis. The two-phase (vaso-obliteration followed by vasoproliferation) theory outlines the evaluation of cytokines in a time-dependent manner. Levels of cytokines may even differ between the blood and the vitreous. Data from animal models of oxygen-induced retinopathy are also valuable. Although conventional cryotherapy and laser photocoagulation are well established and anti-vascular endothelial growth factor agents are available, less destructive novel therapeutics that can precisely target the signaling pathways are required. Linking the cytokines involved in ROP to other maternal and neonatal diseases and conditions provides insights into the management of ROP. Suppressing disordered retinal angiogenesis via the modulation of hypoxia-inducible factor, supplementation of insulin-like growth factor (IGF)-1/IGF-binding protein 3 complex, erythropoietin, and its derivatives, polyunsaturated fatty acids, and inhibition of secretogranin III have attracted the attention of researchers. Recently, gut microbiota modulation, non-coding RNAs, and gene therapies have shown promise in regulating ROP. These emerging therapeutics can be used to treat preterm infants with ROP.

Corneal topography in preterm children aged 2 years to 12 years with or without retinopathy of prematurity.

OBJECTIVES: To evaluate corneal topography in full-term and preterm children with or without retinopathy of prematurity (ROP). METHODS: We enrolled children aged from 2 years to 12 years between January 2019 and May 2021 in the following four groups: full-term (group 1), premature without ROP (group 2), untreated premature with ROP (group 3), and laser-treated and/or intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF)-treated premature with ROP (group 4). Corneal topography was measured with the Galilei Placido-dual Scheimpflug analyzer G4 every half year, and was compared among the groups using generalized estimating equation models at approximately 7 years of age. RESULTS: We included 77, 178, 45, and 131 participants in groups 1, 2, 3, and 4, respectively. The mean (standard deviation) number of visits per patient was 2.9 (1.4). Compared with full-term eyes, premature eyes demonstrated steeper anterior corneal curvature (p = 0.016 and p = 0.008 for the mean and steep K, respectively), higher anterior and posterior corneal astigmatism (p = 0.036 and p = 0.016, respectively), and thinner thinnest pachymetry (p < 0.001). The laser-treated ROP eyes displayed steeper anterior corneal curvature (p = 0.040 for steep K) and higher anterior corneal astigmatism (p = 0.005) than the IVI-treated eyes. Moreover, they exhibited high cone location and magnitude index (1.96) reaching the cut-off for detecting keratoconus (1.82). CONCLUSIONS: The premature status led to greater corneal ectasia, and laser treatment for ROP caused further corneal steepness. Higher anterior corneal astigmatism was associated with laser treatment. The ROP pathology and IVI anti-VEGF treatment exerted a marginal effect on corneal topography.

Neurodevelopmental Outcomes for Retinopathy of Prematurity: A Taiwan Premature Infant Follow-up Network Database Study.

PURPOSE: To evaluate the neurodevelopmental outcomes in premature infants who received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections to treat retinopathy of prematurity (ROP). DESIGN: Retrospective cohort study. METHODS: This study was conducted using the database from the Taiwan Premature Infant Follow-up Network. Demographic data, systemic risk factors, ROP status, and neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) were collected. Patients were divided into 4 groups: prematurity without ROP, ROP without treatment, ROP with laser treatment, and ROP with intravitreal anti-VEGF treatment. A generalized estimating equation was used for analyzing repeated measurements of Bayley-III at the corrected ages of 6, 12, and 24 months. RESULTS: A total of 2090 patients with a mean gestational age of 31.2 weeks were included. The Bayley-III composite scores of patients with ROP treated with anti-VEGF were comparable to those of patients with ROP without treatment (cognitive: P = .491; language: P = .201; motor: P = .151) and premature patients without ROP (cognitive: P = .985; language: P = .452; motor: P = .169) after adjusting for confounders. Patients with ROP treated with laser photocoagulation exhibited poorer cognitive composite scores than did those without treatment (P < .001), premature patients without ROP (P < .001), and those treated with anti-VEGF (P < .001), but they had similar language and motor composite scores. CONCLUSIONS: Intravitreal anti-VEGF treatment for ROP was not associated with adverse neurodevelopment in premature infants. Further studies are needed to determine whether general anesthesia or sedation used in laser treatment for ROP has significant impacts on neurodevelopmental outcomes.

Effects of TIMP-2 Polymorphisms on Retinopathy of Prematurity Risk, Severity, Recurrence, and Treatment Response.

Tissue inhibitors of metalloproteinases (TIMPs) play a crucial role in endogenous angiogenesis besides the regulation of matrix metalloproteinase (MMP) activity. Associations between TIMP-2 gene polymorphisms and the risk of retinopathy of prematurity (ROP) were examined. Premature infants born between 2009 and 2018 were included. Five single-nucleotide polymorphisms (SNPs) of TIMP-2 were analyzed with real-time polymerase chain reaction (PCR). Multivariate logistic regression was applied to model associations between TIMP-2 polymorphisms and ROP susceptibility and severity. The GA+AA genotype in individuals with the TIMP-2 polymorphism of rs12600817 was associated with a higher risk of ROP (odds ratio [OR]: 1.518, 95% confidence interval [CI]: 1.028-2.242) compared with their wild-type genotypes. The AA genotype (OR: 1.962, 95% CI: 1.023-3.762) and the AA+GA genotype (OR: 1.686, 95% CI: 1.030-2.762) in individuals with the rs12600817 polymorphism had higher risks of severe, treatment-requiring ROP relative to their wild-type counterparts. In patients with treatment-requiring ROP, the AG+GG genotypes in the TIMP-2 polymorphism of rs2889529 were correlated with the treatment response (p = 0.035). The TIMP-2 polymorphism of rs12600817 help in predicting ROP risks in preterm infants, while the polymorphism of rs2889529 can serve as a genetic marker in evaluating the ROP treatment response.

Subspecies Classification and Comparative Genomic Analysis of Lactobacillus kefiranofaciens HL1 and M1 for Potential Niche-Specific Genes and Pathways.

(1) Background: Strains HL1 and M1, isolated from kefir grains, have been tentatively identified, based on their partial 16S rRNA gene sequences, as Lactobacillus kefiranofaciens. The two strains demonstrated different health benefits. Therefore, not only the genetic factors exerting diverse functionalities in different L. kefiranofaciens strains, but also the potential niche-specific genes and pathways among the L. kefiranofaciens strains, should be identified. (2) Methods: Phenotypic and genotypic approaches were employed to identify strains HL1 and M1 at the subspecies level. For the further characterization of the probiotic properties of both strains, comparative genomic analyses were used. (3) Results: Both strains were identified as L. kefiranofaciens subsp. kefirgranum. According to the COG function category, dTDP-rhamnose and rhamnose-containing glycans were specifically detected in the L. kefiranofaciens subsp. Kefirgranum genomes. Three unique genes (epsI, epsJ, and epsK) encoding glycosyltransferase in the EPS gene cluster, and the ImpB/MucB/SamB family protein encoding gene were found in HL1 and M1. The specific ability to degrade arginine via the ADI pathway was found in HL1. The presence of the complete glycogen metabolism (glg) operon in the L. kefiranofaciens strains suggested the importance of glycogen synthesis to enable colonization in kefir grains and extend survival under environmental stresses. (4) Conclusions: The obtained novel information on the potential genes and pathways for polysaccharide synthesis and other functionalities in our HL1 and M1 strains could be applied for further functionality predictions for potential probiotic screening.

Infection Sources and Klebsiella pneumoniae Antibiotic Susceptibilities in Endogenous Klebsiella Endophthalmitis.

Endogenous endophthalmitis is an uncommon intraocular infection with potentially devastating consequences on vision. Klebsiella pneumoniae is highly prevalent in East Asian countries, with an increasing incidence recently worldwide. This retrospective study investigates infection sources and antibiotic susceptibilities of K. pneumoniae in patients with endogenous K. pneumoniae endophthalmitis (EKE) in Northern Taiwan. One hundred and fifty-seven patients with EKE were reviewed between January 1996 and April 2019. Pyogenic liver abscess (120/157, 76.4%) was the most common infection source, followed by pneumonia (13, 8.3%), urinary tract infection (7, 4.5%), and intravenous drug use (4, 2.5%). Bilateral involvement was identified in 12.1% (19/157) of patients, especially in patients with pyogenic liver abscess (16/120, 13.3%), pneumonia (2/13, 15.4%), and urinary tract infection (1/7, 14.3%). The antibiotic susceptibility rates were 98.1%, 92.5%, 97.5%, 96.8%, 100%, 99.3%, and 100% for amikacin, cefuroxime, ceftazidime, ceftriaxone, carbapenems, ciprofloxacin, and levofloxacin, respectively. Four extended-spectrum ß-lactamase-producing multidrug-resistant (MDR) K. pneumoniae isolates were identified. In conclusion, pyogenic liver abscess was the major infection source in EKE. In addition, K. pneumoniae was still highly susceptible to ceftazidime and amikacin, and the MDR K. pneumoniae isolates were not common in EKE.

Endogenous Fungal Endophthalmitis: Causative Organisms, Treatments, and Visual Outcomes.

Endogenous fungal endophthalmitis (EFE) is a vision-threatening intraocular infection and a rare complication of fungemia. Early diagnosis and prompt aggressive treatment are crucial to avoid vision loss. We retrospectively reviewed the data of 37 patients (49 eyes) with EFE who were treated at a tertiary referral hospital from January 2000 to April 2019. The most common risk factor was diabetes (24 patients; 65%), followed by recent hospitalization, urinary tract disease, liver disease, and immunosuppressive therapy. Two or more risk factors were detected in 24 patients (65%), and yeasts (29 patients; 78%) were more commonly detected than mold (8 patients; 22%). The most common fungal isolates were Candida spp. (78%), especially Candida albicans (70%). Moreover, 24 eyes in 21 patients underwent vitrectomy, and 2 eyes underwent evisceration. Retinal detachment (RD) occurred in 17 eyes (35%) in 14 patients, and eyes without RD exhibited significantly superior visual outcomes (p = 0.001). A comparison of the initial VA between the better (20/200 or better) and worse groups (worse than 20/200) revealed that better initial VA was related to a superior visual outcome (p = 0.003). Therefore, to achieve superior visual outcomes, early diagnosis and prompt treatment are necessary for patients with EFE.

Mechanism of Glucose Water as a Neural Injection: A Perspective on Neuroinflammation.

The entrapment of peripheral nerves is associated with chronic neuroinflammation and neuropathic pain, and perineural injection therapy with glucose is emerging as an effective treatment for peripheral entrapment neuropathy. However, the mechanism underlying the pharmacological effect of glucose on nerves remains unclear. One of the hypothesized mechanisms is that glucose reduces neurogenic inflammation. Therefore, we investigated the effects of high glucose concentrations on cytokine-induced neuroinflammation in vitro. Human SH-SY5Y neuronal cells were challenged with 10 ng/mL TNF-α for 16 h and subsequently treated with different glucose concentrations (0-25 mM) for 24 h. Cell viability was evaluated using the diphenyltetrazolium bromide assay, and proinflammatory cytokine levels were assessed using ELISA and quantitative PCR. In addition, mRNA levels of NF-κB and cyclooxygenase-2 were analyzed using quantitative PCR. Exposure to 10 ng/mL TNF-α resulted in decreased viability of SH-SY5Y cells and significant upregulation of IL-6, IL-1ß, NF-κB, and cyclooxygenase-2. Subsequent exposure to high glucose levels (25 mM) markedly reduced the upregulation of IL-6, IL-1ß, cyclooxygenase-2, and NF-κB, and restored the functional metabolism of SH-SY5Y cells, compared with that of the normal glucose control. Our findings suggest that high glucose concentrations can mitigate TNF-α-induced NF-κB activation, upregulation of proinflammatory cytokines, and metabolic dysfunction.

Foveal hypoplasia and characteristics of optical components in patients with familial exudative vitreoretinopathy and retinopathy of prematurity.

There has been limited research regarding the status of foveal hypoplasia and the characteristics of the optical components of the eye in patients with familial exudative vitreoretinopathy (FEVR) and retinopathy of prematurity (ROP). In this retrospective cohort study, patients were classified into five groups: patients with stage 1 and 2 FEVR (FEVR group), patients with ROP who received treatment (treated ROP group), patients with ROP who did not receive treatment (untreated ROP group), patients without ROP who had been born preterm (preterm group), and healthy patients who had been born at term (full-term group). Visual acuity, refractive error, characteristics of the optical components, and features of the fovea were compared. In total, 179 eyes from 100 patients were included. Patients in the FEVR group had the highest degrees of myopia (p < 0.001). The axial length of patients in the FEVR group was significantly longer than that of patients in the treated and untreated ROP, preterm, and full-term groups (p < 0.001, p < 0.001, p = 0.001, and p = 0.003, respectively). Patients in the FEVR group had a higher proportion of grade 4 foveal hypoplasia and thinner foveae than those in the other groups (p < 0.001). Patients with FEVR had significantly greater myopic change than patients with ROP; the significantly longer axial length of the FEVR group might be the reason for the greater myopic change and lesser macular thickness. Patients in the FEVR group had more foveal hypoplasia than those in the other groups.

Factors Affecting the Intraluminal Therapy for Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) can be eradicated immediately while conducting an endoscopic examination. The eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95) via local application of single-dose medicament containing amoxicillin, metronidazole, and clarithromycin. We aimed to evaluate factors affecting ILTHPI and to assess the efficacy among single antibiotics, and compared our results with combined antibiotics. We enrolled H. pylori-infected treatment-naïve symptomatic patients; 95 completed triple-antibiotic ILTHPI were evaluated for risk factors, along with 60 completed mono-antibiotic ILTHPI containing amoxicillin, clarithromycin, or metronidazole in each of the 20 patients. Univariate analysis revealed the significant influence of BMI (OR: 1.15; 95% CI: 1.03-1.27, p = 0.011) and gastric juice pH (OR: 1.35; 95% CI: 1.16-1.58, p = 0.0001). Logistic regression analysis also showed significant influence of gastric juice pH (OR: 1.30; 95% CI: 1.10-1.54, p = 0.002). The eradication rate of mono-antibiotic ILTHPI is significantly lower than triple-antibiotic ILTHPI (11.7% vs. 53.7%; p < 0.0001; α = 0.05, power = 1.0). The efficacy was 20% (4/20) for metronidazole, 10% (2/20) for amoxicillin, and 5% (1/20) for clarithromycin. In conclusion, the level of gastric juice pH is a crucial factor affecting the ILTHPI. The detection of gastric juice pH and selection of optimal intraluminal medicaments are important. Further studies with combined antibiotics for ILTHPI, perhaps metronidazole-containing medicaments, are recommended.

Lactobacillus rhamnosus GKLC1 ameliorates cisplatin-induced chronic nephrotoxicity by inhibiting cell inflammation and apoptosis.

Sustained usage of the chemotherapeutic drug cisplatin may lead to chronic kidney disease (CKD). Despite cisplatin being toxic to the kidneys, the efficiency of its therapeutic effects cannot be completely replaced with other drugs. Probiotics can produce various strain-specific health-promoting effects and suppress many specific diseases. In this study, we present the alleviation of cisplatin-induced CKD with a probiotic, Lactobacillus rhamnosus GKLC1. Intermittent low doses of cisplatin were given to male CB57BL/6 mice (n = 6), which induced CKD symptoms such as weight loss, lesions in kidney tissue, and increases in blood urea nitrogen (BUN) and creatinine (CRE) in serum. The rats received two weeks of L. rhamnosus GKLC1 orally at doses of 125, 250, and 500 mg/kg B.W./day. After the treatment, significant dose-dependent reductions were observed in the kidney index, histopathological scoring, serum BUN, and CRE. An LLC-PK1 kidney cell assay revealed that L. rhamnosus GKLC1 suppressed the nephrotoxicity of cisplatin by reducing the inflammation via the MAPKs/NF-ĸB/COX-2 pathway, inhibiting apoptosis via the p53/Bax/Caspase-3 pathway, and ameliorating fibrosis via the STAT3 pathway. We conclude that L. rhamnosus GKLC1 could be applied as an agent to ameliorate the development of CKD.

Treatment responses for branch retinal vein occlusion predicted by semi-automated fluorescein angiography quantification.

BACKGROUNDS: Branch retinal vein occlusion (BRVO) is one of the most important causes of visual loss in retinal vascular diseases. The aim of this study is to predict the treatment response of anti-vascular endothelial growth factor (anti-VEGF) therapy in BRVO using semi-automated quantified fluorescein angiography (FA) features. METHODS: This retrospective case-control study enrolled patients with BRVO who are receiving anti-VEGF therapy and have been followed up for > 1 year. Those receiving < 5 anti-VEGF injections in the first year were classified as the responsive group, while those receiving ≥5 injections were the refractory group. The FA images were subjected to semi-automated pre-processing. Fluorescein leakages at the 5-min image were represented by mean gray value over parafoveal and perifoveal regions. FA leakages and central retinal thickness (CRT) on optical coherence tomography (OCT) were used for predicting the treatment response and compared using area under receiver operating characteristic curve (AUC). RESULTS: Eighty-nine patients (56 males, 33 females, mean age 62.5 ± 10.9 years) with BRVO were enrolled. Of the 89 eyes, 47 (53%) were in the responsive group and 42 (47%) were in the refractory group. The refractory group had a significantly higher number of anti-VEGF injections in the first year (5.9 ± 1.6 versus 2.4 ± 1.2, p < 0.001) when compared with that of the responsive group. It had thicker pre-treatment CRT (p = 0.011), post-treatment best CRT (p < 0.001) and CRT at 1-year (p < 0.001). It also had a higher mean gray value over the parafoveal (p < 0.001) and the perifoveal (p < 0.001) regions. The mean gray value over perifoveal (AUC 0.846) and parafovel (AUC 0.818) had significantly larger AUC than that of the pre-treatment OCT (AUC 0.653; p = 0.005 and p = 0.016, respectively) when predicting treatment response. CONCLUSION: The refractory group had a more severe fluorescein leakage over the parafoveal and the perifoveal regions than the responsive group had. Semi-automated quantified FA leakage can be used as a biomarker for the prediction of anti-VEGF treatment response in macular edema due to BRVO.