Post-stroke dizziness, depression and anxiety.

OBJECTIVE: Vestibular and psychiatric disorders are very closely related. Previous research shows that the discomfort and dysfunction caused by dizziness in patients can affect psychological processes, leading to anxiety and depression, and the irritation of anxiety and depression can aggravate the discomfort of dizziness. But the causal relationship between dizziness in the recovery period of stroke and Post-stroke depression (PSD) / Post-stroke anxiety (PSA) is not clear. Identifying the causal relationship between them can enable us to conduct more targeted treatments. METHODS: We review the epidemiology and relationship of dizziness, anxiety, and depression, along with the related neuroanatomical basis. We also review the pathophysiology of dizziness after stroke, vestibular function of patients experiencing dizziness, and the causes and mechanisms of PSD and PSA. We attempt to explore the possible relationship between post-stroke dizziness and PSD and PSA. CONCLUSION: The treatment approach for post-stroke dizziness depends on its underlying cause. If the dizziness is a result of PSD and PSA, addressing these psychological factors may alleviate the dizziness. This can be achieved through targeted treatments for PSD and PSA, such as psychotherapy, antidepressants, or anxiolytics, which could indirectly improve dizziness symptoms. Conversely, if PSA and PSD are secondary to vestibular dysfunction caused by stroke, a thorough vestibular function assessment is crucial. Identifying the extent of vestibular impairment allows for tailored interventions. These could include vestibular rehabilitation therapy and medication aimed at vestibular restoration. By improving vestibular function, secondary symptoms like anxiety and depression may also be mitigated.

Microbulbifer bruguierae sp. nov., isolated from sediment of mangrove plant Bruguiera sexangula, and comparative genomic analyses of the genus Microbulbifer.

A Gram-negative, non-motile, strictly aerobic, rod-shaped bacterium, designated as H12T, was isolated from the sediments of mangrove plant Bruguiera sexangula taken from Dapeng district, Shenzhen, PR China. The pairwise 16S rRNA gene sequence analysis showed that strain H12T shared high identity levels with species of the genus Microbulbifer, with the highest similarity level of 98.5 % to M. pacificus SPO729T, followed by 98.1 % to M. donghaiensis CN85T. Phylogenetic analysis using core-genome sequences showed that strain H12T formed a cluster with type species of M. pacificus SPO729T and M. harenosus HB161719T. The complete genome of strain H12T was 4 481 396 bp in size and its DNA G+C content was 56.7 mol%. The average nucleotide identity and digital DNA-DNA hybridization values among strain H12T and type species of genus Microbulbifer were below the cut-off levels of 95-96 and 70 %, respectively. The predominant cellular fatty acids of strain H12T were iso-C15 : 0 (22.5 %) and C18 : 1 ω7c (13.9 %). Ubiquinone-8 was detected as the major respiratory quinone. The polar lipids of strain H12T comprised one phosphatidylglycerol, one phosphatidylethanolamine, one unidentified aminoglycophospholipid, one unidentified glycophospholipid, three unidentified glycolipids, two unidentified aminolipids, and one unidentified lipid. Based on polyphasic evidence, strain H12T represents a novel species of the genus Microbulbifer, for which the name Microbulbifer bruguierae sp. nov. is proposed. The type strain is H12T (=KCTC 92859T=MCCC 1K08451T). Comparative genomic analyses of strain H12T with strains of the genus Microbulbifer reveal its potential in degradation of pectin.

The effect of intraocular lens and lens eye on the treatment of macular splits in high myopia.

BACKGROUND: Macular retinoschisis in patients with high myopia is one of the main reasons for a decline in visual function and the perceived deformation of visual objects. OBJECTIVE: This study aimed to investigate the therapeutic effect of cataract phacoemulsification and foldable intraocular lens implantation (FILI) combined with internal limiting membrane stripping (ILMS) in the treatment of macular retinoschisis in patients with high myopia. METHODS: A total of 52 patients (55 eyes) who had been diagnosed with macular retinoschisis with high myopia between June 2019 and June 2020 were enrolled in the present study. Patients in the control group (25 eyes) received 23G vitreous surgery and macular ILMS and long-term inert gas (C3F8) filling of the vitreous cavity; patients in the research group (30 eyes) were additionally treated with cataract phacoemulsification and soft intraocular lens on the same treatment basis as the control group. RESULTS: The difference in average BCVA between the control and the research groups was not statistically significant before the surgery (P> 0.05) but was statistically significant 12 months after the procedure (P< 0.05). The minimum foveal thickness was significantly decreased in the two groups after the surgery compared with before the procedure (P< 0.05). CONCLUSION: Cataract phacoemulsification and FILI further improved the therapeutic effect of ILMS in the treatment of macular retinoschisis in patients with high myopia.

Long-term effects of transcranial direct current stimulation (tDCS) combined with speech language therapy (SLT) on post-stroke aphasia patients: A systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation tool for improving language performance in patients with aphasia after stroke. However, it remains unclear whether it has long-term effects. After consulting a large number of relevant studies, it was found that there are no definitive conclusions about the long-term effects of tDCS on post-stroke aphasia patients. OBJECTIVE: To determine whether tDCS has long-term effects on post-stroke aphasia patients (PAPs) and which type of tDCS has the most beneficial treatment effects on language performance (especially naming ability). METHODS: A network meta-analysis was conducted by searching for randomized controlled trials (RCTs) published until April 2023 in the following databases: Web of Science, Embase, Medline (from OVID and PubMed), PsycInfo and PsycARTICLES (from OVID). We only included RCTs published in English. PAPs treated by tDCS combined with speech-language therapy were selected. Sham tDCS was the control group. Naming ability or other language performance must be assessed at follow-up states. Two reviewers independently used checklists to assess the primary outcome (the long-term effects on naming ability) and the secondary outcome (other language performance, such as communication). Cochrane Collaboration guidelines were used to assess the risk of bias. RESULTS: Seven studies with 249 patients were included for data synthesis. For primary outcomes (naming nous), there was no obvious evidence to show a difference between interventions (C-tDCS vs. S-tDCS SMD = 0.06, 95% CI = -1.01, 1.12; A-tDCS vs. S-tDCS SMD = 0.00, 95% CI = -0.66, 0.65; D-tDCS vs. S-tDCS SMD = 0.77, 95% CI = -0.71, 2.24; A-tDCS vs. C-tDCS SMD = -0.06, 95% CI = -1.31,1.19; D-tDCS vs. C-tDCS SMD = 0.71, 95% CI = -1.11,2.53; D-tDCS vs. A-tDCS SMD = 0.77, 95% CI = -0.84, 2.39). In addition, no evidence showed differences in communication ability (C-tDCS vs. S-tDCS SMD = 0.08 95% CI = -1.77, 1.92; A-tDCS vs. S-tDCS SMD = 1.23 95% CI = -1.89, 4.34; D-tDCS vs. S-tDCS SMD = 0.70; 95% CI = -1.93, 3.34; A-tDCS vs. C-tDCS SMD = 1.15 95% CI = -2.48, 4.77; D-tDCS vs. C-tDCS SMD = 0.62 95% CI = -2.59, 3.84; D-tDCS vs. A-tDCS SMD = -0.52 95% CI = -4.60, 3.56). CONCLUSION: It seems that tDCS has no long-term effects on post-stroke aphasia patients in naming nouns and communication in terms of the results of our network meta-analysis. However, the results should be interpreted with caution. In the future, more RCTs with long follow-up times should be included in the research to conduct subgroup or meta-regression analyses to obtain a sufficient effect size.

DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway.

CDK4/6 are important regulators of cell cycle and their inhibitors have been approved as anti-cancer drugs. Here, we report a STING-dependent anti-tumor immune mechanism responsible for tumor suppression by CDK4/6 blockade. Clinical datasets show that in human tissues, CDK4 and CDK6 are over-expressed and their expressions are negatively correlated with patients' overall survival and T cell infiltration. Deletion of Cdk4 or Cdk6 in tumor cells significantly reduce tumor growth. Mechanistically, we find that Cdk4 or Cdk6 deficiency contributes to an increased level of endogenous DNA damage, which triggers the cGAS-STING signaling pathway to activate type I interferon response. Knockout of Sting is sufficient to reverse and partially reverse the anti-tumor effect of Cdk4 and Cdk6 deficiency respectively. Therefore, our findings suggest that CDK4/6 inhibitors may enhance anti-tumor immunity through the STING-dependent type I interferon response.

Internal limiting membrane peeling combined with mouse nerve growth factor injection for idiopathic macular hole.

BACKGROUND: The study was intended to confirm whether Pars Plana Vitrectomy (PPV) with Internal Limiting Membrane (ILM) peeling and intravitreal injection mouse Nerve Growth Factor(mNGF) was effective for the treatment of Idiopathic Macular Hole(IMH) by Optical Coherence Tomography Angiography(OCTA) and microperimetry. METHODS: A retrospective study was performed in adults' patients. A total of 44 eyes (March 2021-October 2021) with IMH who received surgical treatment in the Affiliated Eye Hospital of Nanchang University in Nanchang City, Jiangxi Province were selected. The subjects were treated using PPV combined with ILM peeling and intravitreal mNGF (combined group) or PPV combined with ILM peeling (placebo group). The Best Corrected Visual Acuity (BCVA), Optical Coherence Tomography Angiography (OCTA) and MP-3 microperimetry were carried out and observed at baseline, 1 week(1W), 1,3 and 6 months (1 M,3 M,6 M) postoperatively. RESULTS: The minimum diameter of MH were (568.650 ± 215.862)µm and (533.348 ± 228.836)µm in the Placebo and Combine group pre-operative. During the observation, the macular hole closure rate in the placebo group and combined group were 90% and 95.8% respectively and the difference was not statistically significant(p = 0.583). Compared to pre-surgery, the perimeter and circularity of Foveal Avascular Zone (FAZ) in the placebo group decreased at 1,3,6 M (p = 0.001, < 0.001, < 0.001) and 1W,1,6 M (p = 0.045,0.010, < 0.001) post-surgery respectively. And the perimeter and circularity of FAZ showed significant reduction in the combined group at 1,3,6 M (p = 0.005,0.004, < 0.001) and at each follow-up time point (all values of p < 0.001). The vascular density of SCP increased at 1W(p = 0.031) and 6 M(p = 0.007), the perfusion density of SCP was significantly improved at each follow-up time point (p = 0.028, 0.011, 0.046, 0.004) in the combined group. The BCVA in the combined group was more obvious than that in the placebo group at 1 M, 3 M and 6 M after operation (t1 = 2.248, p1 = 0.030; t3 = 3.546, p3 = 0.001; t6 = 3.054, p6 = 0.004). The changes of BCVA in the combined group was more conspicuous than that in the placebo group at each follow-up time point, and the difference was statistically significant (t1 = 2.206,p1 = 0.033;t2 = 2.54,p2 = 0.015;t3 = 3.546,p3 = 0.001;t6 = 3.124,p6 = 0.003).At 1 M, 3 M and 6 M, the MRS of 2° and 4° in the combined group was better than that in the placebo group(t = -2.429,-2.650,-3.510,-2.134,-2.820,-3.099 p = 0.020,0.011,0.001,0.039,0.007,0.004). During various time points, the MRS of 12°in the combined group was better than that in the placebo group, the difference was statistically significant (t = -3.151, -3.912, -4.521, -4.948, p1 = 0.003, < 0.001, < 0.001 < 0.001). The integrity of External Limiting Membrane (ELM) in combination group was better than that in placebo group at 6 M postoperative(p = 0.022) and that of Ellipsoid Zone(EZ) was preferable in the combined group at 3 M and 6 M after surgery(p = 0.012,0.004). Correlation analysis showed that the integrity of EZ was correlated with 12°MRS at 1 M, 3 M and 6 M after surgery(r = -0.318, -0.343,-0.322;p = 0.023,0.033, < 0.001). There was no correlation between postoperative ELM integrity and postoperative BCVA and 12°MRS(p > 0.05). CONCLUSIONS: Our results manifested that PPV combined with ILM peeling and intravitreal injection mNGF might be more effective for initial IMH. This method increased the blood flow, MRS and promoted the recovery of ELM and EZ in the macular and might improve the visual function of patients postoperatively.

Associations of non-traditional cardiovascular risk factors and body mass index with metabolic syndrome in the Chinese elderly population.

BACKGROUND: Metabolic syndrome (MetS), a clustering of traditional cardiovascular risk factors (CVRF), is currently one of the major global public health burdens. However, associations between MetS and non-traditional CVRF represented by uric acid (UA), homocysteine (HCY) and hypersensitive C-reactive protein (HsCRP) have not been well explored in the elderly population, especially when considering body mass index (BMI). METHODS: Participants from the Shanghai Elderly Cardiovascular Health (SHECH) study cohort in 2017 were analyzed. MetS was defined using the modified American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Logistic regression models were used to assess associations of non-traditional CVRF, BMI with MetS. RESULTS: Of the 4360 participants analyzed, 2378 (54.5%) had MetS, the mean (SD) UA was 331 (86) µmol/L, and the median (IQR) HCY and HsCRP were 15 (13-18) µmol/L and 1.0 (0.5-2.1) mg/L, respectively. Participants with higher non-traditional CVRF tended to have a higher significant risk of MetS (P < 0.001), which did not changed substantially in most population subgroups (P-interaction > 0.05). BMI mediated 43.89% (95%CI: 30.38-57.40%), 37.34% (95% CI: 13.86-60.83%) and 30.99% (95%CI: 13.16-48.83%) of associations of hyperuricemia (HUA), hyperhomocysteinemia (HHCY) and high HsCRP (HHsCRP) with MetS, respectively. Abnormal non-traditional CVRF combined with overweight/obesity greatly increased MetS risk (adjusted OR(95%CI): HUA + Overweight: 5.860(4.059-8.461); 6.148(3.707-10.194); HHCY + Overweight: 3.989(3.107-5.121); HHCY + Obese: 5.746(4.064-8.123); HHsCRP + Overweight: 4.026(2.906-5.580); HHsCRP + Obese: 7.717(4.508-13.210)). CONCLUSIONS: In the Chinese elderly population, HUA, HHCY, and HHsCRP were all significantly and independently associated with MetS, supporting the potential of focusing on non-traditional CVRF interventions for preventing and controlling MetS. BMI played moderate mediating roles in associations between non-traditional CVRF and MetS, and abnormal non-traditional CVRF combined with overweight/obesity had significant synergistic effects on MetS risk, highlighting the importance of better weight management in the elderly population.

Exploring the Effect of the Gut Microbiome on the Risk of Age-Related Macular Degeneration From the Perspective of Causality.

Purpose: To explore the mechanisms relating the gut microbiome (GM) to age-related macular degeneration (AMD), as they remain unclear. GM taxa that appear to act within the gut-retina axis may affect the risk of AMD. Methods: Single-nucleotide polymorphisms (SNPs) of 196 GM taxa were obtained from the MiBioGen consortium, and a Mendelian randomization (MR) study was carried out to estimate the causality between GM taxa and AMD (defined as an endpoint based on ICD-9 and ICD-10). Using the data from the FinnGen consortium (6157 patients and 288,237 controls), we explored the GM taxa for causality and verified the results at the replication stage based on the MRC-IEU consortium (3553 cases and 147,089 controls). Inverse variance weighting (IVW) was the main method used to analyze causality, and the MR results were verified using heterogeneity tests and pleiotropy tests. Results: According to the MR results, order Rhodospirillales (P = 3.38 × 10-2), family Victivallaceae (P = 3.14 × 10-2), family Rikenellaceae (P = 3.58 × 10-2), genus Slackia (P = 3.15 × 10-2), genus Faecalibacterium (P = 3.01 × 10-2), genus Bilophila (P = 1.11 × 10-2), and genus Candidatus Soleaferrea (P = 2.45 × 10-2) were suggestively associated with AMD. In the replication stage, only order Rhodospirillales (P = 0.03) passed validation. The heterogeneity (P > 0.05) and pleiotropy (P > 0.05) tests in two stages confirmed the robustness of the MR results. Conclusions: We confirmed that order Rhodospirillales influenced the risk of AMD based on the gut-retina axis, providing new impetus for the development of the GM as an intervention to prevent the occurrence and development of AMD.

Description and genomic characterization of Gallaecimonas kandeliae sp. nov., isolated from the sediments of mangrove plant Kandelia obovate.

The genus Gallaecimonas, proposed by Rodríguez-Blanco et al. (Int J Syst Evol Microbiol 60:504-509, 2010), is mainly isolated from marine environments. So far, only three species have been identified and characterized in this genus. In this study, a new Gallaecimonas strain named Q10T was isolated from the sediments of mangrove plant Kandelia obovate taken from Dapeng district, Shenzhen, China. Strain Q10T was a Gram-stain-negative, non-motile, strictly aerobic, rod-shaped bacterium, and grew with 0-8.0% (w/v) NaCl, at 10-45 °C and at pH 5.5-8.5. Phylogenetic analysis indicated that strain Q10T and the three Gallaecimonas species formed a clade in the tree, with 16S rRNA gene sequence similarities ranging from 96.0 to 97.0%. The major respiratory quinone is Q8. The polar lipids comprised aminolipid, aminophospholipid, diphosphatidylglycerol, glycolipid, phosphatidylethanolamine, phosphatidylglycerol, glycophospholipid and phospholipid. The predominant fatty acids are C16:0, C17:1ω8c, summed feature 3 (C16:1ω7c/C16:1ω6c), and iso-C16:0. The complete genome of strain Q10T is 3,836,841 bp with a G+C content of 62.6 mol%. The orthologous proteins analysis revealed 55 unique proteins in strain Q10T related to important biological processes, especially three frataxins related to iron-sulfur cluster assembly, which may play a pivotal role in environmental adaptability of this species. Based on polyphasic taxonomic data, strain Q10T is considered to represent a novel species within the genus Gallaecimonas, for which the name Gallaecimonas kandelia sp. nov. is proposed. The type strain is Q10T (=KCTC 92860T=MCCC 1K08421T). These results contribute to a better understanding of general features and taxonomy of the genus Gallaecimonas.

The role of aldosterone in the pathogenesis of diabetic retinopathy.

Aldosterone, as a mineralocorticoid of adrenal origin, has effects that are not limited to the urinary tract. As an important regulator in Vasoactive hormone pathways, aldosterone may play an effect in the pathogenesis of diabetic retinopathy (DR) through the regulation of oxidative stress, vascular regulation, and inflammatory mechanisms. This implies that mineralocorticoids, including aldosterone, have great potential and value for the diagnosis and treatment of DR. Because early studies did not focus on the intrinsic association between mineralocorticoids and DR, targeted research is still in its infancy and there are still many obstacles to its application in the clinical setting. Recent studies have improved the understanding of the effects of aldosterone on DR, and we review them with the aim of exploring possible mechanisms for the treatment and prevention of DR.

Prevalence, Associated Factors, and Appropriateness of Empirical Treatment of Trichomoniasis, Bacterial Vaginosis, and Vulvovaginal Candidiasis among Women with Vaginitis.

Trichomoniasis (TV), bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) are the most common causes of vaginitis. This study investigated the prevalence of these diagnoses, their associated factors, and the appropriateness of the empirical treatment. From March 25, 2019, to June 17, 2022, 429 women with symptoms or signs of vaginitis were enrolled in a hospital in northern Taiwan with 438 episodes of vaginitis. Vaginal swabs were collected for Gram's staining, in vitro cultures for Trichomonas vaginalis, bacteria, and yeasts, and multiplex PCR assay for TV, BV, and VVC. Their empirical treatments were recorded. Factors associated with different etiologies of vaginitis were sought in multivariable logistic regression models. The prevalence of TV, BV, and VVC were 2.1%, 22.8%, and 21.7%, respectively, while coinfections of BV and VVC, TV and BV, TV and VVC, and triple infection occurred in 5.0%, 0.2%, 0.2%, and 0.7%, respectively. Multivariable analyses revealed that having multiple sexual partners was associated with TV and BV (adjusted odds ratio [aOR] 9.756 and 3.246, respectively), while menopausal women were less likely to have VVC (aOR 0.184). Moreover, dysuria was associated with TV (aOR 4.981), vaginal itch and pelvic pain with VVC (aOR 3.223 and 0.425, respectively), and discharge pH > 4.5 with BV (aOR 1.767). Other clinical symptoms and pelvic examination features had limited value for differential diagnosis. Among the 78 empirical antifungal and metronidazole prescriptions, 55.2% were ineffective or unnecessary. Our study highlights the importance to integrate appropriate diagnostic tools into the clinical care of women with vaginitis. IMPORTANCE Vaginal complaints are widespread among women and are associated with emotional, physical, and economic burdens with challenges in their diagnosis and management. In this survey, we identified that 40% of vaginitis in Taiwan was caused by either trichomoniasis, bacterial vaginosis, vulvovaginal candidiasis, or a combination of these infections. Our data suggested that typical physical findings appeared infrequently among women with these infections and their empirical treatments were frequently inappropriate. Our findings highlighted the importance of integrating proper diagnostic tools into clinical practice to improve the diagnosis and management of vaginitis, as recommended by national and international guidelines.

Comparative genomic analysis provides insights into taxonomy and temperature adaption of Aeromonas salmonicida.

Aeromonas salmonicida has long been known as psychrophiles since it is mainly isolated from cold water fish, and recent reports have revealed the existence of mesophilic strains isolated from warm sources. However, the genetic differences between mesophilic and psychrophilic strains remain unclear due to few complete genomes of mesophilic strain are available. In this study, six A. salmonicida (2 mesophilic and 4 psychrophilic) were genome-sequenced, and comparative analyses of 25 A. salmonicida complete genomes were conducted. The ANI values and phylogenetic analysis revealed that 25 strains formed three independent clades, which were referred as typical psychrophilic, atypical psychrophilic and mesophilic groups. Comparative genomic analysis showed that two chromosomal gene clusters, related to lateral flagella and outer membrane proteins (A-layer and T2SS proteins), and insertion sequences (ISAs4, ISAs7 and ISAs29) were unique to the psychrophilic groups, while the complete MSH type IV pili were unique to the mesophilic group, all of which may be considered as lifestyle-related factors. The results of this study not only provide new insights into the classification, lifestyle adaption and pathogenic mechanism of different strains of A. salmonicida, but also contributes to the prevention and control of disease caused by psychrophilic and mesophilic A. salmonicida.

Gut microbiota dysbiosis associated with different types of demyelinating optic neuritis in patients.

BACKGROUND: Demyelinating optic neuritis (DON) causes rapid vision loss in young and middle-aged people. The limited efficacy of treatment and the toxic side effects of drugs significantly affect the quality of life of patients with DON. Therefore, DON pathogenesis has always been a research hotspot in terms of prevention and treatment. Studies have suggested that gut microbiota imbalances may be involved in autoimmune disease development via the modulation of multiple inflammatory cytokines and anti-inflammatory metabolites. Therefore, this study aims to explore gut microbiota differences between healthy controls (HCs) and patients with DON. METHODS: A total of 54 patients with DON and 41 HCs were recruited. Fecal and blood samples were collected before and after intravenous methylprednisolone pulse (IVMP) treatment. The Shannon index, gut microbiota structure, and differential bacteria were evaluated and compared. RESULTS: The Shannon diversity index was decreased in patients with DON (p < 0.001) but was higher after IVMP treatment (p < 0.05). In patients with DON, Blautia, Escherichia-Shigella, and Ruminococcus showed higher abundances, whereas Bacteroides, Faecalibacterium, Roseburia, Parabacteroides, Romboutsia, and Alistipes showed lower abundances compared to that in the HCs. After IVMP treatment, the Shannon index of the myelin oligodendrocyte glycoprotein-immunoglobulin G (+) (MOG-IgG (+)) and both aquaporin-4 (AQP4)-IgG (-) and MOG-IgG (-) groups increased (p < 0.05). Bacteroides was negatively correlated with interleukin (IL)-21, IL-17E, and tumor necrosis factor-α levels (p < 0.05, r = -0.54; p < 0.05, r= -0.50; p < 0.05, r =-0.55, respectively). Escherichia was positively correlated with macrophage inflammatory protein-3α (p < 0.05, r = 0.51). Alistipes was negatively correlated with soluble CD40 ligand (p < 0.05, r = -0.52). CONCLUSION: The gut microbiota differed significantly between patients with DON and HCs; however, IVMP treatment may restore gut microbiota diversity and structure in patients with DON. Moreover, gut microbiota changes may play a role in DON pathogenesis.

TFEB attenuates hyperglycemia-induced retinal capillary endothelial cells injury via autophagy regulation.

Diabetic retinopathy is a common microvascular complication of diabetes mellitus. The maintenance of retinal capillary endothelial cell homeostasis requires a complete and unobtrusive flow of autophagy because it may help combat the inflammatory response, apoptosis, and oxidative stress damage of cells in diabetes mellitus. The transcription factor EB is a master regulator of autophagy and lysosomal biogenesis, but its role in diabetic retinopathy remains unknown. This study aimed to confirm the involvement of transcription factor EB in diabetic retinopathy and explore the role of transcription factor EB in hyperglycemia-linked endothelial injury in vitro. First, the expression levels, including the nuclear location of transcription factor EB and autophagy, were reduced in diabetic retinal tissues and high glucose-treated human retinal capillary endothelial cells. Subsequently, autophagy was mediated by transcription factor EB in vitro. Moreover, transcription factor EB overexpression reversed high glucose-induced autophagy inhibition and lysosomal dysfunction and protected human retinal capillary endothelial cells from inflammation, apoptosis, and oxidative stress damage caused by high glucose treatment. Additionally, under high-glucose stimulation, the autophagy inhibitor chloroquine attenuated transcription factor EB overexpression-mediated protection, and the autophagy agonist Torin1 rescued transcription factor EB knockdown-induced damage effects. Taken together, these results suggest that transcription factor EB is involved in the development of diabetic retinopathy. In addition, transcription factor EB protects human retinal capillary endothelial cells from high glucose-induced endothelial damage via autophagy.

Liposomes loaded with dual clinical photosensitizers for enhanced photodynamic therapy of cervical cancer.

Photodynamic therapy (PDT) has become a potential anti-cancer strategy owing to its negligible invasiveness, low toxicity, and high selectivity. The photosensitizer (PS) plays an indispensable role in PDT. Herein, a novel type of PS (Ce6-MB@Lips) which can be excited by a near-infrared (NIR) laser was designed and synthesized. Methylene blue (MB) and Chlorin e6 (Ce6), two organic dyes approved by the Food and Drug Administration (FDA), were used to prepare Ce6-MB@Lips by thin-film dispersion method, which improve the water solubility of Ce6 and reduce the cytotoxicity of MB. The Ce6-MB@Lips were shown to have a spherical nanostructure with an average particle size of 160.3 nm and excellent water solubility. Then the optical properties of Ce6-MB@Lips were further studied. Ce6-MB@Lips showed absorption peaks at 413 nm/670 nm and fluorescence peak at 697 nm. Compared with Ce6@Lips and MB@Lips, Ce6-MB@Lips showed better stability, stronger fluorescence intensity, and higher singlet oxygen (1O2) generation ability. Cell experimental analysis exhibited that the stable Ce6-MB@Lips showed low cytotoxicity, high phototoxicity and high reactive oxygen species (ROS) production capacity. After effective cell internalization, the prepared Ce6-MB@Lips showed excellent ability to promote tumor cell apoptosis in vitro. The Ce6-MB@Lips could be a promising candidate for PDT of cervical cancer.

Direct administration of mesenchymal stem cell-derived mitochondria improves cardiac function after infarction via ameliorating endothelial senescence.

Mitochondrial dysfunction is considered to be a key contributor to the development of heart failure. Replacing injured mitochondria with healthy mitochondria to restore mitochondrial bioenergy in myocardium holds great promise for cardioprotection after infarction. This study aimed to investigate whether direct transplantation of exogenous mitochondria derived from mesenchymal stem cells (MSC-mt) is beneficial and superior in protecting cardiac function in a mouse model of myocardial infarction (MI) compared to mitochondria derived from skin fibroblast (FB-mt) and to explore the underlying mechanisms from their effects on the endothelial cells. The isolated MSC-mt presented intact mitochondrial morphology and activity, as determined by electron microscopy, JC-1 mitochondrial membrane potential assay, and seahorse assay. Direct injection of MSC-mt into the peri-infarct region in a mouse MI model enhanced blood vessel density, inhibited cardiac remodeling and apoptosis, thus improving heart function compared with FB-mt group. The injected MSC-mt can be tracked in the endothelial cells. In vitro, the fluorescence signal of MSC-mt can be detected in human umbilical vein endothelial cells (HUVECs) by confocal microscopy and flow cytometry after coculture. Compared to FB-mt, MSC-mt more effectively protected the HUVECs from oxidative stress-induced apoptosis and reduced mitochondrial production of reactive oxygen species. MSC-mt presented superior capacity in inducing tube formation, enhancing SCF secretion, ATP content and cell proliferation in HUVECs compared to FB-mt. Mechanistically, MSC-mt administration alleviated oxidative stress-induced endothelial senescence via activation of ERK pathway. These findings suggest that using MSCs as sources of mitochondria is feasible and that proangiogenesis could be the mechanism by which MSC-mt transplantation attenuates MI. MSC-mt transplantation might serve as a new therapeutic strategy for treating MI.

Mendelian randomization analysis reveals causal relationships between gut microbiome and optic neuritis.

BACKGROUND: It is unclear whether gut microbiota (GM) affects the risk of optic neuritis (ON) through the "gut-brain" axis and the "gut-retina" axis. To examine the causal relationship between GM and ON, we conducted Mendelian randomization (MR) study. METHODS: Up to 18,340 samples of 24 population-based cohorts were included in genome-wide association study (GWAS) of 196 GM taxa. ON outcomes were selected from the FinnGen GWAS (951 ON cases and 307,092 controls). In addition, the GWAS based on UK Biobank (UKB) (105 ON cases and 456,243 controls) was used for further exploration. Inverse variance weighted (IVW) was carried out to estimate their effects on ON risk and the MR assumptions were evaluated in sensitivity analyses. RESULTS: Among the 196 GM taxa, the IVW results confirmed that Family -Peptococcaceae (P = 2.17 × 10-3), Genus- Hungatella (P = 4.57 × 10-3) and genus-Eubacterium_rectale_group (P = 0.02) were correlated with the risk of ON based on Finngen GWAS. Based on data from UKB, Genus- Eubacterium_hallii_group (P = 1.50 × 10-3) and Genus- Ruminococcaceae_UCG_002 (P = 0.02) were correlated with the risk of ON. At the phylum, class and order levels, no GM taxa were causally related to ON (P > 0.05). Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. CONCLUSION: Our MR findings support the causal effect of specific GM taxa on ON. GM may affect the risk of ON through the "gut-brain" axis and the "gut-retina" axis. However, further research is needed to confirm the relevant mechanism of the relationship between GM and ON.

PpIX/IR-820 Dual-Modal Therapeutic Agents for Enhanced PDT/PTT Synergistic Therapy in Cervical Cancer.

High treatment accuracy is the key to efficient cancer treatment. Photodynamic therapy (PDT) and photothermal therapy (PTT) are two kinds of popular, precise treatment methods. The combination of photodynamic and photothermal therapy (PDT/PTT) can greatly enhance the precise therapeutic efficacy. In this work, protoporphyrin IX (PpIX) was selected as the PDT agent (photosensitizer), and new indocyanine green (IR-820) was selected as the PTT agent. Further, the two kinds of theranostic agents were encapsulated by biological-membrane-compatible liposomes to form PpIX-IR-820@Lipo nanoparticles (NPs), a new kind of PDT/PTT agent. The PpIX-IR-820@Lipo NPs exhibited good water solubility, a spherical shape, and high fluorescence peak emission in the near-infrared spectral region (700-900 nm, NIR). The cellular toxicity of PpIX-IR-820@Lipo NPs for human cervical cancer cells (HeLa) and human cervical epithelial cells (H8) was detected by the CCK-8 method, and low cytotoxicity was observed for the PpIX-IR-820@Lipo NPs. Then, the excellent cellular uptake of PpIX-IR-820@Lipo NPs was confirmed by laser scanning confocal microscopy. Moreover, the PDT/PTT property of PpIX-IR-820@Lipo NPs was illustrated via 2',7'-dichlorofluorescin diacetate (DCFH-DA) and annexin V-fluorescein isothiocyanate (annexin V-FITC), as indicator probes. The PDT/PTT synergistic efficiency of PpIX-IR-820@Lipo NPs on HeLa cells was verified, exhibiting a high efficiency of 70.5%. Thus, the novel theranostic PpIX-IR-820@Lipo NPs can be used as a promising PDT/PTT synergistic theranostic nanoplatform in future cervical cancer treatment.

Integrative analyses of a mitophagy-related gene signature for predicting prognosis in patients with uveal melanoma.

We aimed to create a mitophagy-related risk model via data mining of gene expression profiles to predict prognosis in uveal melanoma (UM) and develop a novel method for improving the prediction of clinical outcomes. Together with clinical information, RNA-seq and microarray data were gathered from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ConsensusClusterPlus was used to detect mitophagy-related subgroups. The genes involved with mitophagy, and the UM prognosis were discovered using univariate Cox regression analysis. In an outside population, a mitophagy risk sign was constructed and verified using least absolute shrinkage and selection operator (LASSO) regression. Data from both survival studies and receiver operating characteristic (ROC) curve analyses were used to evaluate model performance, a bootstrap method was used test the model. Functional enrichment and immune infiltration were examined. A risk model was developed using six mitophagy-related genes (ATG12, CSNK2B, MTERF3, TOMM5, TOMM40, and TOMM70), and patients with UM were divided into low- and high-risk subgroups. Patients in the high-risk group had a lower chance of living longer than those in the low-risk group (p < 0.001). The ROC test indicated the accuracy of the signature. Moreover, prognostic nomograms and calibration plots, which included mitophagy signals, were produced with high predictive performance, and the risk model was strongly associated with the control of immune infiltration. Furthermore, functional enrichment analysis demonstrated that several mitophagy subtypes may be implicated in cancer, mitochondrial metabolism, and immunological control signaling pathways. The mitophagy-related risk model we developed may be used to anticipate the clinical outcomes of UM and highlight the involvement of mitophagy-related genes as prospective therapeutic options in UM. Furthermore, our study emphasizes the essential role of mitophagy in UM.

Polydopamine encapsulated new indocyanine green theranostic nanoparticles for enhanced photothermal therapy in cervical cancer HeLa cells.

Photothermal therapy (PTT) has attracted extensive attention in cancer treatment due to its non-invasiveness, high efficiency, and repeatability in recent years. Photothermal agents (PTAs) are the key factor for PTT. Recently, although an increasing number of PTAs have been developed, there is still a great demand for optimized photothermal nanoparticles (NPs) with low toxicity, bio-safety and stability. Herein, new indocyanine green (IR820) with near-infrared (NIR:700-1,700 nm) fluorescence emission was selected as a photothermal agent (PTA). To enhance the PTT property, IR820 was encapsulated with another kind of PTA, polydopamine (PDA) under alkaline conditions. Furthermore, to improve the biocompatibility of the NPs, methoxy polyethylene glycol amine (mPEG-NH2) was modified via a Michael addition to form a novel kind of IR820@PDA@PEG NPs. After detailed characterization and analysis, the obtained IR820@PDA@PEG NPs showed a spherical shape with an average diameter of ∼159.6 nm. Meanwhile, the formed IR820@PDA@PEG NPs exhibited better photostability and lower cytotoxicity than free IR820 molecules. The photothermal performance of IR820@PDA@PEG NPs was further analyzed in vitro, and the temperature of IR820@PDA@PEG NPs (100 µg/ml) reached 54.8°C under 793 nm laser irradiation. Afterwards, the cellular uptake of IR820@PDA@PEG NPs was evaluated via confocal laser scanning fluorescence microscopic imaging. Then, PTT experiments on HeLa cells demonstrated that IR820@PDA@PEG NPs can hyperthermal ablate cancer cells (∼49.1%) under 793 nm laser irradiation. Therefore, IR820@PDA@PEG NPs would be a promising PTA for the treatment of cervical cancer HeLa cells.