Revolutionizing eye care: the game-changing applications of nano-antioxidants in ophthalmology.

Since the theory of free radical-induced aging was proposed in 1956, it has been constantly proven that reactive oxygen species (ROS) produced by oxidative stress play a vital role in the occurrence and progression of eye diseases. However, the inherent limitations of traditional drug therapy hindered the development of ophthalmic disease treatment. In recent years, great achievements have been made in the research of nanomedicine, which promotes the rapid development of safe theranostics in ophthalmology. In this review, we focus on the applications of antioxidant nanomedicine in the treatment of ophthalmology. The eye diseases were mainly classified into two categories: ocular surface diseases and posterior eye diseases. In each part, we first introduced the pathology of specific diseases about oxidative stress, and then presented the representative application examples of nano-antioxidants in eye disease therapy. Meanwhile, the nanocarriers that were used, the mechanism of function, and the therapeutic effect were also presented. Finally, we summarized the latest research progress and limitations of antioxidant nanomedicine for eye disease treatment and put forward the prospects of future development.

Influence of Gut Microbiota and its Metabolites on Progression of Metabolic Associated Fatty Liver Disease.

Metabolic associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes. Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD. Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms, identify diagnostic markers, and develop drugs or probiotics for the treatment of MAFLD. Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.

TMEM25 inhibits monomeric EGFR-mediated STAT3 activation in basal state to suppress triple-negative breast cancer progression.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.

Acupuncture inhibits mammalian target of rapamycin, promotes autophagy and attenuates neurological deficits in a rat model of hemorrhagic stroke.

BACKGROUND: Intracerebral hemorrhage (ICH) accounts for approximately 15% of all stroke cases. Previous studies suggested that acupuncture may improve ICH-induced neurological deficits. Therefore, we investigated the effects of acupuncture on neurological deficits in an animal model of ICH. METHODS: Adult male Sprague-Dawley rats were injected with autologous blood (50 µL) into the right caudate nucleus. Additional rats underwent sham surgery as controls. ICH rats either received acupuncture (GV20 through GB7 on the side of the lesion) or sham acupuncture (1 cm to the right side of the traditional acupuncture point locations). Some ICH rats received acupuncture plus rapamycin injection into the right lateral ventricle. Neurological deficits in the various groups were assessed based on composite neurological score. The perihemorrhagic penumbra was analyzed by histopathology following hematoxylin-eosin staining. Levels of autophagy-related proteins light chain (LC)3 and p62 as well as of mammalian target of rapamycin (mTOR)-related proteins, and phosphorylated (p)-mTOR and p-S6K1 (ribosomal protein S6 kinase beta-1), were assessed by Western blotting. RESULTS: Acupuncture significantly improved composite neurological scores 7 days after ICH (17.7 ± 1.49 vs 14.8 ± 1.32, p < 0.01). Acupuncture augmented autophagosome and autolysosome accumulation based on transmission electron microscopy. Acupuncture significantly increased expression of LC3 (p < 0.01) but decreased expression of p62 (p < 0.01). Acupuncture also reduced levels of p-mTOR and p-S6K1 (both p < 0.01). CONCLUSION: Acupuncture improved neurological deficits in a rat model of ICH, possibly by inhibiting the mTOR pathway and activating autophagy.

Measurement of ozone deposition velocity onto human surfaces of Chinese residents and estimation of corresponding production of oxidation products.

China has been experiencing a sharp increase in outdoor ozone concentration. The deposition velocity of ozone onto human surfaces strongly affects the indoor ozone concentration, and the production of oxidation products. In this study, we measured the deposition velocity of ozone onto human surfaces in six Chinese residential rooms, each housing 1-3 occupants. In addition, we estimated the corresponding emission rate of oxidation products. The measured mean value of the deposition velocity is 14.8 (±10.1) m/h, which is close to those reported in earlier studies in western countries. We also find that the ozone deposition velocity onto human surfaces is positively correlated to the weighted duration from the last laundry and bath/facial-cleansing, and it is negatively correlated to the relative humidity of the indoor air. The estimated emission rates of 6-MHO, 4-OPA, acetone, geranyl acetone, 1,4-butanedial decanal, and all gas-phase products are 7.7 × 1016, 6.7 × 1016, 9.4 × 1016, 9.7 × 1015, 1.3 × 1016, 3.4 × 1016, and 4.8 × 1017 molecule per person h-1, respectively, with an indoor ozone concentration of 5 ppb at steady state. The measured deposition velocity of ozone onto human surfaces of Chinese residents, and the emission rates of the corresponding oxidation products may be applied for the estimation of human exposure to ozone and its oxidation products in China.

Heart injury signs are associated with higher and earlier mortality in coronavirus disease 2019 (COVID-19)

ImportanceHeart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. ObjectiveTo explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and ParticipantsA single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. ExposuresHigh levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; -HBDH). Main Outcomes and MeasuresMortality in hospital and days from admission to mortality (survival days). ResultsOf 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21[~]83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission ([≥] 6.126 pg/mL), even within the clinical normal range (0[~]28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4+ and CD8+ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and -HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and -HBDH on admission were associated with higher mortality. Both high LDH and -HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days (r= -0.42, 95% CI= -0.64[~]-0.12, P=0.005). LDH level on admission was negatively correlated with survival days (r= -0.35, 95% CI= -0.59[~]-0.05, P=0.022). Conclusions and RelevanceHeart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury. Key pointsO_ST_ABSQuestionC_ST_ABSDoes coronavirus disease 2019 (COVID-19) cause heart injury and hereby impact mortality? FindingsIn this retrospective cohort study including 188 patients with COVID-19, patients with high levels of high-sensitivity cardiac troponin I (hs-TNI) on admission had significantly higher mortality (50.0%) than patients with moderate or low levels of hs-TNI (10.0% or 9.1%). hs-TNI level on admission was significantly negatively correlated with survival days (r= -0.42, 95% CI= -0.64[~]-0.12, P=0.005). MeaningCOVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, in order to maximally prevent or rescue heart injury-related mortality in COVID-19.

[Penetrative needling improves neurological function by up-regulating expression of autophagy related protein LC3 in rats with hemorrhagic stroke].

OBJECTIVE: To observe the effect of penetrative needling from "Baihui" (GV20) to "Qubin" (GB7) on neurological function and expression of autophagy related protein microtubule-associated protein, light chain 3 (LC3) in rats with hemorrhagic stroke, so as to explore its mechanism underlying improvement of hemorrhagic stroke. METHODS: A total of 120 male SD rats were randomly divided into sham operation, model, non-acupoint, acupuncture and medication (Rapamycin) groups which were further divided into two time-point subgroups (3, 7 days after modeling, n=12/subgroup). The intracerebral hemorrhage model was established by injection of the rat's auto-blood (50 µL) into the putaman region. Penetrative needling from GV20 to GB7 or sham acupoints (about 1 cm beside GV20 and GB7) was conducted for 30 min, twice daily for 7 days. For rats of the medication group, Rapamycin solution (7 µmol/L) was injected into the right lateral ventricle. The neurological functions (locomotor and balance deficits) were evaluated according to suspended wire test (0-6 points) and horizontal board walking test (0-6 points). Immunohistochemistry and Western blot were used to detect the expression of total LC3 and expression of LC3-Ⅰ and LC3-Ⅱ proteins in the ischemic penumbra region of brain tissue, respectively. RESULTS: After modeling, the neurological function scores were significantly decreased on day 3 and 7, the levels of LC3-Ⅱ/Ⅰ and LC3 protein on day 3 and 7 were significantly increased in the model group relevant to the sham operation group (P<0.05). Following the interventions, the neurological function scores as well as LC3-Ⅱ/Ⅰ and LC3 protein expression were significantly increased in both acupuncture and medication groups compared with the model group (P<0.05). The effect of Rapamycin was obviously stronger than that of penetrative needling in up-regulating the expression of LC3-Ⅱ/Ⅰ and LC3 protein (P<0.05). CONCLUSION: Penetrative needling can improve neurologic function in hemorrhagic stroke rats, which is related with its effect in up-regulating the expression of autophagy-related protein LC3.

Anesthetic isoflurane posttreatment attenuates experimental lung injury by inhibiting inflammation and apoptosis.

We investigated the effect of 1.4% isoflurane (ISO) on the development of inflammation and apoptosis caused by zymosan (ZY) in mice. We found that ZY-challenged mice exhibited significant body weight loss, markedly high mortality, and significant lung injury characterized by the deterioration of histopathology, histologic scores, and wet-to-dry ratio after ISO treatment. ISO dramatically attenuated ZY-induced lung neutrophil recruitment and inflammation, as evidenced by the reduced levels of total cells, neutrophils, and proinflammatory cytokines (i.e., tumor necrosis factor- α , interleukin- (IL-) 1 ß , IL-6, and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid and of their mRNA expression in lung tissues. ISO also inhibited ZY-induced expression and activation of nuclear factor-kappaB p65 and inducible nitric oxide synthase in pulmonary tissue. ZY administration also resulted in the upregulation of heme oxygenase-1 expression and activity in the lung, which was further enhanced by ISO treatment. Moreover, ISO markedly prevented ZY-induced pulmonary cell apoptosis in mice, as reflected by the decrease in expression of procaspase-8, procaspase-3, cleaved caspase-8, and cleaved caspase-3, as well as in caspase-3 activity and Bcl-2-associated X/B-cell lymphoma 2 ratio. These results indicate that ISO is a potential therapeutic drug for treating ZY-induced lung injury, and further investigations are warranted.

Dry eye syndrome in elderly Tibetans at high altitude: a population-based study in China.

PURPOSE: To determine the prevalence of dry eye syndrome, analyze the relationship between dry eye symptoms and signs, and identify associated risk factors for dry eye syndrome in an elderly Tibetan population at high altitude. METHODS: A population-based survey was conducted from October 2006 to December 2006. A stratified, clustered, random sampling procedure was used to select 2632 native Tibetan people >or=40 years of age. Symptoms of dry eye were assessed by using a 6-item validated questionnaire. Dry eye syndrome was diagnosed in those subjects having 1 or more symptoms often or all the time. Positive signs included a tear film breakup time of or=1. Correlations between symptoms and signs were analyzed. RESULTS: Of a total of 2632 eligible subjects, 2229 (84.69%) were examined. The data of 1840 participants were analyzed. Of 1840 participants, 52.4% (95% confidence interval: 50.2-54.7) were symptomatic. The tear film breakup time of or=1 was seen in 5.8% (95% confidence interval: 4.7-6.9). The correlations between dry eye symptoms and signs were statistically significant. Independent risk factors for dry eye syndrome were positive dry eye signs, increased age, low education level and socioeconomic status, and higher altitude. CONCLUSIONS: This study shows a high prevalence rate of dry eye syndrome in elderly Tibetans, representing an important health problem.

Pterygium in Tibetans: a population-based study in China.

PURPOSE: To describe the prevalence and to identify associated risk factors for pterygium in a Tibetan population at high altitude in Zeku County, China. METHODS: A prospective population-based survey was conducted from October to December 2006. A stratified, clustered, randomized sampling procedure was used to select 2632 Tibetan people aged 40 years and older. Pterygium was diagnosed and graded clinically as grade 1 (transparent), 2 (intermediate) and 3 (opaque). Risks factors associated with pterygium were evaluated with logistic regression models. RESULTS: From a total of 2632 eligible subjects, 2229 (84.69%) were examined. There were 323 people with pterygium, equivalent to an overall prevalence of 14.49% (95% confidence interval [CI] 13.03-15.95). Pterygium was independently associated with increasing age for persons aged 70-79 years, compared with those aged 40-49 years (odds ratio [OR] 2.0; 95% CI 1.4-2.8), female gender (OR 1.6; 95% CI 1.2-2.0), dry eye symptoms (OR 1.3; 95% CI 1.0-1.7), seldom use of sunglasses/crystal spectacles (OR 4.6; 95% CI 1.9-11.3) or hats (OR 3.6: 95% CI 2.4-5.4), lower education level (<3 years) (OR 1.6; 95% CI 1.1-2.4) and low socioeconomic status (OR 1.9; 95% CI 1.5-2.4). CONCLUSIONS: The prevalence of pterygium in a Tibetan population at high altitude is significantly high, particularly in certain at-risk groups. The primary causative factors are related to ocular sun exposure, which are easily preventable. Public health schemes to address this serious health issue are urgently needed.