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1.
Medicine (Baltimore) ; 99(7): e19075, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32049809

RESUMO

BACKGROUND: Accumulating pre-clinical and clinical studies suggested that the renin-angiotensin system blockers (RASBs) possess anti-carcinogenic properties, and their use is associated with favorable outcomes in many types of cancers. METHODS: A systematic literature search of relevant databases through January 2019 was conducted to identify studies assessing the RASBs on prognostic outcomes in digestive system malignancies patients on the basis of predetermined selection criteria for pooled hazard ratio (HR) with 95% confidence intervals (CIs). A total of 13 studies were included in the meta-analysis. RESULTS: The meta-analysis showed that the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) resulted in a significant improvement in overall survival (HR 0.79; 95%CI 0.70-0.89; P < .000), cancer-specific survival (HR 0.81; 95%CI 0.73-0.90; P < .000) and recurrence-free survival (HR 0.68; 95%CI 0.54-0.85; P = .001), but not progression-free survival (HR 0.88; 95%CI 0.73-1.07; P = .183) and disease-free survival (HR 0.50; 95%CI 0.11-2.39; P = .103). Subgroup analysis indicated that the use of RASBs has a significant improvement of overall survival (OS) in pancreatic cancer, liver cancer, and gastric cancer. Two studies evaluated the dose-response relationship between ACEIs/ARBs therapy and survival and showed higher doses and better survival [(1-364 defined daily doses: odds ratio (OR) 0.89, 95%CI 0.78-1.01, P = .076), (≥365 defined daily doses: OR 0.54, 95%CI: 0.24-1.24, P = .148]. CONCLUSIONS: Meta-analysis of studies supports a beneficial association between use of RASBs and survival of digestive system malignancies.

2.
J Immunol ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32034062

RESUMO

Microglia play essential roles in neuroinflammatory responses after traumatic brain injury (TBI). Our previous studies showed that phenotypes of microglia, as well as infiltrating macrophages, altered at different stages after CNS injury, which was correlated to functional outcomes. IL-13 is an anti-inflammatory cytokine that has been reported to protect against demyelination and spinal cord injury through immunomodulation. The effects of IL-13 in microglia/macrophage-mediated immune responses after TBI remain unknown. In this study, we showed that intranasal administration of IL-13 in male C57BL/6J mice accelerated functional recovery in the controlled cortical impact model of TBI. IL-13 treatment increased the time to fall off in the Rotarod test, reduced the number of foot faults in the foot fault test, and improved the score in the wire hang test up to 28 d after TBI. Consistent with functional improvement, IL-13 reduced neuronal tissue loss and preserved white matter integrity 6 d after TBI. Furthermore, IL-13 ameliorated the elevation of proinflammatory factors and reduced the number of proinflammatory microglia/macrophages 6 d after TBI. Additionally, IL-13 enhanced microglia/macrophage phagocytosis of damaged neurons in the peri-lesion areas. In vitro studies confirmed that IL-13 treatment inhibited the production of proinflammatory cytokines in rat primary microglia in response to LPS or dead neuron stimulation and increased the ability of microglia to engulf fluorophore-labeled latex beads or dead neurons. Collectively, we demonstrated that IL-13 treatment improved neurologic outcomes after TBI through adjusting microglia/macrophage phenotypes and inhibiting inflammatory responses. IL-13 may represent a potential immunotherapy to promote long-term recovery from TBI.

3.
Life Sci ; : 117424, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057900

RESUMO

AIMS: Dysfunction of the Hippo-Yes-Associated Protein (YAP) signaling pathway is known to be associated with hepatocellular carcinoma (HCC). Evodiamine (Evo), a plant-derived bioactive alkaloid, exerts inhibitory effects on cancer. However, the precise influence of Evo on HCC and its potential effects on Hippo-YAP signaling have yet to be ascertained. Here, the effects of Evo on cell proliferation and apoptosis were evaluated using HCC cell lines (HepG2 and Bel-7402) and nude mice with xenograft tumors. We further investigated whether Evo exerts anti-HCC activity through effects on Hippo-YAP signaling in vitro with the aid of XMU-MP-1, an inhibitor of the key component of this pathway, mammalian sterile 20-like kinase 1/2. MAIN METHODS: Cell proliferation and apoptosis were assessed using 5-ethynyl-2'-deoxyuridine staining, colony formation, flow cytometry, hematoxylin-eosin and dUTP nick-end labeling experiments. Bioinformatics and real-time quantitative polymerase chain reaction (RT-qPCR) arrays were performed to determine the associations among Evo, HCC progression and the Hippo-YAP pathway. The expression patterns of components of Hippo-YAP signaling and apoptotic genes were further examined via RT-qPCR and immunoblotting. KEY FINDINGS: Evo inhibited proliferation and promoted apoptosis of HCC cell lines in vitro, and attenuated xenograft tumor formation in nude mice in vivo. Mechanistically, Evo treatment stimulated the Hippo-YAP signaling pathway. In vitro, the effects of Evo on HCC cell proliferation and apoptosis were alleviated by XMU-MP-1. SIGNIFICANCE: Our collective results revealed that the anti-HCC effects of Evo were correlated with the Hippo-YAP signaling pathway.

5.
EBioMedicine ; 52: 102652, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32058942

RESUMO

BACKGROUND: Alteration of commensal bacterial composition is associated with many inflammatory diseases. However, few studies have pinpointed the specific bacterial genes that may suppress host immune responses against microbes and maintain homeostasis in the host intestine. METHODS: High-throughput screening was performed in Caenorhabditis elegans with a single gene knockout ut screening was performed in Caenorhabditis elegans with a single gene knockout Escherichia coli (E. coli) library and identified the immune suppression gene blc. The coding sequences of blc among different kinds of E. coli strains were aligned to identify the single nucleotide polymorphisms (SNPs). Physiological and biochemical experiments were performed in C. elegans and mice to explore the function of the blc variant. FINDINGS: By screening 3983 E. coli mutants, we discovered that 9 bacterial genes, when deleted, activate innate immunity in the host C. elegans. Among these 9 genes, the gene encoding blc showed a distinctive SNP in many clinically pathogenic bacteria. We found that bacteria with this SNP, which converts Blc G84 to Blc E84, are highly enriched in the faeces of patients with inflammatory bowel disease (IBD). Exposure to BlcE84-encoding bacteria resulted in epithelial barrier disruption and immune activation in both worms and mice. Detailed analysis indicated that infection with BlcE84-encoding bacteria causes a significant decrease in LPE levels in the intestine and subsequently disrupts gut epithelial integrity in mice. Consistently, the levels of LPE in patients with IBD are significantly lower than those in healthy people. Finally, supplementation with LPE, which activates LPA1/PLCß/PKC signaling, reversed the defects induced by BlcE84-encoding bacteria. INTERPRETATION: Our results identified a novel bacterial gene, blc, in E. coli that regulates host gut integrity and immunity. FUND: The Ministry of Science and Technology of China; the National Natural Science Foundation of China; and the Natural Science Foundation of Jiangsu Province.

6.
Acta Pharmacol Sin ; 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949293

RESUMO

Thromboembolic disease is a common cardio-cerebral vascular disease that threatens human life and health. Thrombin not only affects the exogenous coagulation pathway, but also the endogenous pathway. Thus, it becomes one of the most important targets of anticoagulant drugs. RGD-hirudin is an anticoagulant drug targeting thrombin, but it can only be administered intravenously. We designed a low molecular weight peptide based on RGD-hirudin that could prevent blood clots. We first used NMR to identify the key amino acid residues of RGD-hirudin that interacted with thrombin. Then, we designed a novel direct thrombin inhibitor peptide (DTIP) based on the structure and function of RGD-hirudin using homology modeling. Molecular docking showed that the targeting and binding of DTIP with thrombin were similar to those of RGD-hirudin, suggesting DTIP interacted directly with thrombin. The active amino acids of DTIP were identified by alanine scanning, and mutants were successfully constructed. In blood clotting time tests in vitro, we found that aPTT, PT, and TT in the rat plasma added with DTIP were greatly prolonged than in that added with the mutants. Subcutaneous injection of DTIP in rats also could significantly prolong the clotting time. Thrombelastography analysis revealed that DTIP significantly delayed blood coagulation. Bio-layer interferometry study showed that there were no significant differences between DTIP and the mutants in thrombin affinity constants, suggesting that it might bind to other sites of thrombin rather than to its active center. Our results demonstrate that DTIP with low molecular weight can prevent thrombosis via subcutaneous injection.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31981518

RESUMO

BACKGROUND: Colonoscopy performance varies among endoscopists, impairing the discovery of colorectal cancers and precursor lesions. We aimed to construct a real-time quality improvement system (ENDOANGEL) to monitor real-time withdrawal speed and colonoscopy withdrawal time and to remind endoscopists of blind spots caused by endoscope slipping. We also aimed to evaluate the effectiveness of this system for improving adenoma yield of everyday colonoscopy. METHODS: The ENDOANGEL system was developed using deep neural networks and perceptual hash algorithms. We recruited consecutive patients aged 18-75 years from Renmin Hospital of Wuhan University in China who provided written informed consent. We randomly assigned patients (1:1) using computer-generated random numbers and block randomisation (block size of four) to either colonoscopy with the ENDOANGEL system or unassisted colonoscopy (control). Endoscopists were not masked to the random assignment but analysts and patients were unaware of random assignments. The primary endpoint was the adenoma detection rate (ADR), which is the proportion of patients having one or more adenomas detected at colonoscopy. The primary analysis was done per protocol (ie, in all patients having colonoscopy done in accordance with the assigned intervention) and by intention to treat (ie, in all randomised patients). This trial is registered with http://www.chictr.org.cn, ChiCTR1900021984. FINDINGS: Between June 18, 2019, and Sept 6, 2019, 704 patients were randomly allocated colonoscopy with the ENDOANGEL system (n=355) or unassisted (control) colonoscopy (n=349). In the intention-to-treat population, ADR was significantly greater in the ENDOANGEL group than in the control group, with 58 (16%) of 355 patients allocated ENDOANGEL-assisted colonoscopy having one or more adenomas detected, compared with 27 (8%) of 349 allocated control colonoscopy (odds ratio [OR] 2·30, 95% CI 1·40-3·77; p=0·0010). In the per-protocol analysis, findings were similar, with 54 (17%) of 324 patients assigned ENDOANGEL-assisted colonoscopy and 26 (8%) of 318 patients assigned control colonoscopy having one or more adenomas detected (OR 2·18, 95% CI 1·31-3·62; p=0·0026). No adverse events were reported. INTERPRETATION: The ENDOANGEL system significantly improved the adenoma yield during colonoscopy and seems to be effective and safe for use during routine colonoscopy. FUNDING: Hubei Provincial Clinical Research Center for Digestive Disease Minimally Invasive Incision, Hubei Province Major Science and Technology Innovation Project, and the National Natural Science Foundation of China.

8.
ChemSusChem ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31943844

RESUMO

Two-dimensional (2D) nanomaterials have drawn a wide range of research interests because of their unique ultrathin layered structures and attractive properties. Especially, the electrochemical properties and great variety of 2D nanomaterials make they are highly attractive candidates for electrochemical capacitors (ECs), such as supercapacitors, lithium ion capacitors and sodium ion capacitors. Herein, we provide a comprehensive review on recent progress towards the applications of 2D nanomaterials for electrochemical capacitors. Several typical types of 2D nanomaterials were first briefly introduced, followed with the detailed descriptions on their electrochemical capacitors applications. Finally, the research perspectives and the future research directions of these interesting areas are also provided.

9.
J Cell Physiol ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31898815

RESUMO

C terminus of Hsc70-interacting protein (CHIP) is a chaperone-dependent and U-box containing E3 ubiquitin ligase. In previous studies, we found that CHIP regulates the stability of multiple tumor necrosis factor receptor-associated factor proteins in bone cells. In Chip global knockout (KO) mice, nuclear factor-κB signaling is activated, osteoclast formation is increased, osteoblast differentiation is inhibited, and bone mass is decreased in postnatal Chip KO mice. To determine the role of Chip in different cell types at different developmental stages, we created Chipflox/flox mice. We then generated Chip conditional KO mice ChipCMV and ChipOsxER and demonstrated defects in skeletal development and postnatal bone growth in Chip conditional KO mice. Our findings indicate that Chip conditional KO mice could serve as a critical reagent for further investigations of functions of CHIP in bone cells and in other cell types.

10.
Nat Commun ; 11(1): 479, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980602

RESUMO

Congenital scoliosis (CS) is a complex genetic disorder characterized by vertebral malformations. The precise etiology of CS is not fully defined. Here, we identify that mutation in dual serine/threonine and tyrosine protein kinase (dstyk) lead to CS-like vertebral malformations in zebrafish. We demonstrate that the scoliosis in dstyk mutants is related to the wavy and malformed notochord sheath formation and abnormal axial skeleton segmentation due to dysregulated biogenesis of notochord vacuoles and notochord function. Further studies show that DSTYK is located in late endosomal/lysosomal compartments and is involved in the lysosome biogenesis in mammalian cells. Dstyk knockdown inhibits notochord vacuole and lysosome biogenesis through mTORC1-dependent repression of TFEB nuclear translocation. Inhibition of mTORC1 activity can rescue the defect in notochord vacuole biogenesis and scoliosis in dstyk mutants. Together, our findings reveal a key role of DSTYK in notochord vacuole biogenesis, notochord morphogenesis and spine development through mTORC1/TFEB pathway.

11.
Nat Commun ; 11(1): 484, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980627

RESUMO

ß-Cell dysfunction and reduction in ß-cell mass are hallmark events of diabetes mellitus. Here we show that ß-cells express abundant Kindlin-2 and deleting its expression causes severe diabetes-like phenotypes without markedly causing peripheral insulin resistance. Kindlin-2, through its C-terminal region, binds to and stabilizes MafA, which activates insulin expression. Kindlin-2 loss impairs insulin secretion in primary human and mouse islets in vitro and in mice by reducing, at least in part, Ca2+ release in ß-cells. Kindlin-2 loss activates GSK-3ß and downregulates ß-catenin, leading to reduced ß-cell proliferation and mass. Kindlin-2 loss reduces the percentage of ß-cells and concomitantly increases that of α-cells during early pancreatic development. Genetic activation of ß-catenin in ß-cells restores the diabetes-like phenotypes induced by Kindlin-2 loss. Finally, the inducible deletion of ß-cell Kindlin-2 causes diabetic phenotypes in adult mice. Collectively, our results establish an important function of Kindlin-2 and provide a potential therapeutic target for diabetes.

12.
J Org Chem ; 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31944108

RESUMO

We report the synthesis of C6-substituted isoquinolino[1,2-b]quinazolinones via rhodium(III)-catalyzed C-H annulation with sulfoxonium ylides and evaluation of the cytotoxic activity of the scaffold. This C-H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino[1,2-b]quinazolines reported to date. This operationally simple method is compatible with a wide variety of the sulfoxonium ylide and arene C-H activation coupling partners, permitting access to diverse isoquinolino[1,2-b]quinazolines. This method shows a high atom economy, generating H2O and dimethyl sulfoxide (DMSO) as by-products. This method is scalable and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.

13.
Int J Biol Macromol ; 149: 127-139, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31978476

RESUMO

Uranium (U(VI)) is radioactive and the primary raw material in the production of nuclear energy. Hence the research associated with uranium removal gained a lot of importance because to reduce the threat of uranium contamination to ecology and its environment surroundings. Thus, economically as well as environmentally friendly sorbents with a good sorption capacity have to be acquired for the removal of U(VI) pollutants from the aqueous and polluted sea samples. In this study magnetic- Momordica charantia leaf powder impregnated into chitosan (m-MCLPICS) was prepared through the impregnation method. After preparation the adsorbent undergone through various characterizations such as BET, XRD, FTIR, SEM with elemental mapping, and VSM analysis. The specific surface area (93.12 m2/g), pore size (0.212 cm3/g) and pore volume (15.35 nm) of m-MCLPICS was obtained from the BET analysis. A pH value of 5 and 0.5 g of adsorbent dose were selected as an optimum values for U(VI) removal. Kinetic data follows the pseudo-second-order model, and the equilibrium data fitted well with the Langmuir isotherm model. ΔG° (-1.6999, -2.4994, -3.5476 and -4.5147 kJ/mol), ΔH0 (25.1 kJ/mol) and ΔS0 (0.089 kJ/mol K) indicates that the U(VI) sorption process is feasible, spontaneous and endothermic.

14.
Molecules ; 25(1)2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31948057

RESUMO

Breast cancer has become a worldwide threat, and chemotherapy remains a routine treatment. Patients are forced to receive continuous chemotherapy and suffer from severe side effects and poor prognosis. Natural alkaloids, such as piperine (PP) and piperlongumine (PL), are expected to become a new strategy against breast cancer due to their reliable anticancer potential. In the present study, cell viability, flow cytometry, and Western blot assays were performed to evaluate the suppression effect of PP and PL, alone or in combination. Data showed that PP and PL synergistically inhibited breast cancer cells proliferation at lower doses, while only weak killing effect was observed in normal breast cells, indicating a good selectivity. Furthermore, apoptosis and STAT3 signaling pathway-associated protein levels were analyzed. We demonstrated that PP and PL in combination inhibit STAT3 phosphorylation and regulate downstream molecules to induce apoptosis in breast cancer cells. Taken together, these results revealed that inactivation of STAT3 was a novel mechanism with treatment of PP and PL, suggesting that combination application of natural alkaloids may be a potential strategy for prevention and therapy of breast cancer.

15.
Nat Nanotechnol ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31988508

RESUMO

It has recently been shown that sulfur, a solid material in its elementary form S8, can stay in a supercooled state as liquid sulfur in an electrochemical cell. We establish that this newly discovered state could have implications for lithium-sulfur batteries. Here, through in situ studies of electrochemical sulfur generation, we show that liquid (supercooled) and solid elementary sulfur possess very different areal capacities over the same charging period. To control the physical state of sulfur, we studied its growth on two-dimensional layered materials. We found that on the basal plane, only liquid sulfur accumulates; by contrast, at the edge sites, liquid sulfur accumulates if the thickness of the two-dimensional material is small, whereas solid sulfur nucleates if the thickness is large (tens of nanometres). Correlating the sulfur states with their respective areal capacities, as well as controlling the growth of sulfur on two-dimensional materials, could provide insights for the design of future lithium-sulfur batteries.

16.
Int J Biol Macromol ; 148: 887-897, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31945442

RESUMO

In this study m-AHLPICS (magnetic Arachis hypogaea leaves powder impregnated into chitosan) was prepared and utilized as an adsorbent to remove U(VI) from aqueous and real polluted wastewater samples. m-AHLPICS was characterized by using the BET, XRD, FTIR, SEM with elemental mapping and magnetization measurements. Different experimental effects such as pH, dose, contact time, and temperature were considered broadly. Chitosan modified magnetic leaf powder (m-AHLPICS) exhibits an excellent adsorption capacity (232.4 ± 5.59 mg/g) towards U(VI) ions at pH 5. Different kinetic models such as pseudo-first-order, and pseudo-second-order models were used to know the kinetic data. Langmuir, Freundlich and D-R isotherms were implemented to know the adsorption behavior. Isothermal information fitted well with Langmuir isotherm. Kinetic data followed by the pseudo-second-order kinetics (with high R2 values, i.e., 0.9954, 0.9985 and 0.9971) and the thermodynamic data demonstrate that U(VI) removal using m-AHLPICS was feasible, and endothermic in nature.

17.
Int Ophthalmol ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31894459

RESUMO

PURPOSE: To compare the choroidal thickness (CT) of the affected eyes with the contralateral eyes in the active period and in the remission period in Posner-Schlossman syndrome (PSS) using EDI-OCT. PATIENTS AND METHODS: This prospective longitudinal study included 15 patients with PSS and 15 age- and sex-matched healthy subjects. All subjects underwent complete ophthalmologic examinations, and EDI-OCT was conducted to measure macular CT (mCT) at the subfoveal locations and at 0.5, 1.0 and 2.0 mm superior, inferior, nasal and temporal to the fovea. The mean measurements at each location were used for analysis. Linear regression analysis was performed to analyse the correlation between the choroidal thickness and IOP, and the correlation between the choroidal thickness and episode time. RESULTS: The mean mCT was significantly thinner in affected eyes than in contralateral eyes in the acute phase (p = 0.010) but were not different in the remission phase (p = 0.404). The mean mCT was significantly increased in the remission phase compared to that in the acute phase in the affected eyes (p = 0.000). The mCT of healthy subjects was significantly thicker than in the affected eyes (p = 0.020) and similar to the fellow eyes of PSS patients (p = 0.357) in the acute phase. Linear regression analyses show negative correlations between the mCT changes and IOP changes in the affected eyes compared to those in the fellow eyes in the acute period (R2 = 0.396, p = 0.033) and between the mCT changes and IOP changes from the acute period to the remission period in the affected eyes (R2 = 0.372, p = 0.027). Linear regression analyses show positive correlations (age- and sex-matched) between the CT changes and episode time from the affected eyes to the fellow eyes in the acute period (R2 = 0.492, p = 0.012). CONCLUSIONS: The mCT values of the PSS-affected eyes were significantly thinner than those of the fellow eyes in the acute phase and in the remission phase, and this change was correlated with IOP reduction and episode time.

18.
Artigo em Inglês | MEDLINE | ID: mdl-31917615

RESUMO

RATIONALE: Vascular remodeling, including smooth muscle cell hypertrophy and proliferation, is the key pathological feature of pulmonary arterial hypertension (PAH). Prostaglandin (PG) I2 analogs (baraprost, iloprost, and treprostinil) are effective in the treatment of PAH. Of note, the clinically favorable effects of treprostinil in severe PAH may be attributable to concomitant activation of PGD2 receptor subtype 1 (DP1). OBJECTIVES: To study the role of DP1 in the progression of PAH and its underlying mechanism. METHODS AND RESULTS: DP1 expression was downregulated in hypoxia-treated PASMCs and in pulmonary arteries (PAs) from rodent PAH models and idiopathic PAH patients. DP1 deletion exacerbated PA remodeling in hypoxia-induced PAH, whereas pharmacological activation or forced expression of DP1 receptor had the opposite effect in different rodent models. DP1 deficiency promoted PASMC hypertrophy and proliferation in response to hypoxia via induction of mammalian target of rapamycin complex (mTORC) 1 activity. Rapamycin, an inhibitor of mTORC1, alleviated the hypoxia-induced exacerbation of PAH in DP1-/- mice. DP1 activation facilitated raptor dissociation from mTORC1 complex and suppressed mTORC1 activity through protein kinase A (PKA)-dependent phosphorylation of raptor at Ser791. Moreover, treprostinil treatment blocked the progression of hypoxia-induced PAH in mice in part by targeting DP1 receptor. CONCLUSION: DP1 activation attenuates hypoxia-induced PA remodeling and PAH through PKA-mediated dissociation of raptor from the mTORC1 complex. These results suggest that DP1 receptor may serve as a therapeutic target for the management of PAH.

19.
J Refract Surg ; 36(1): 42-48, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31917850

RESUMO

PURPOSE: To compare the safety of the minimum ophthalmic viscosurgical device (OVD) technique with the standard procedure in phakic Visian Implantable Collamer Lens (ICL) (STAAR Surgical AG, Nidau, Switzerland) implantation. METHODS: This retrospective cohort study evaluated a total of 147 eyes of 74 patients who underwent ICL implantation with the minimum OVD technique (minimum OVD group) and 154 eyes of 77 patients with the standard procedure (standard OVD group). Intraoperative and postoperative complications were recorded. Preoperative and postoperative visual acuity, intraocular pressure (IOP), aqueous depth (AQD), and central corneal endothelial cell density (ECD) were collected and analyzed over the 12-month follow-up. Lens vault and occurrence of paracentesis after surgery were also recorded. RESULTS: No intraocular complications were observed. No difference was found in visual outcomes, lens vault, and AQD at all time points between the two groups (P > .05). The minimum OVD group had significantly lower IOP than the standard OVD group at 2 hours (17.04 ± 4.21 vs 19.40 ± 6.78 mm Hg, P < .001) and 3 hours (15.12 ± 3.38 vs 17.15 ± 5.09 mm Hg, P < .001) postoperatively. The IOP gradually returned to the preoperative level after 24 hours postoperatively. The occurrence rate of paracentesis was significantly less in the minimum OVD group compared with the standard group (0.68% [1 of 147] vs 3.2% [5 of 154], P < .001). ECD was not significantly different between groups at all time points (P > .05). CONCLUSIONS: The minimum OVD technique could achieve visual and structural outcomes comparable to the standard procedure without additional damage to the corneal endothelial cells, while reducing the IOP fluctuations after surgery. [J Refract Surg. 2020;36(1):42-48.].

20.
Nat Commun ; 11(1): 180, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31924779

RESUMO

Macropinocytosis is an evolutionarily-conserved, large-scale, fluid-phase form of endocytosis that has been ascribed different functions including antigen presentation in macrophages and dendritic cells, regulation of receptor density in neurons, and regulation of tumor growth under nutrient-limiting conditions. However, whether macropinocytosis regulates the expansion of non-transformed mammalian cells is unknown. Here we show that primary mouse and human T cells engage in macropinocytosis that increases in magnitude upon T cell activation to support T cell growth even under amino acid (AA) replete conditions. Mechanistically, macropinocytosis in T cells provides access of extracellular AA to an endolysosomal compartment to sustain activation of the mechanistic target of rapamycin complex 1 (mTORC1) that promotes T cell growth. Our results thus implicate a function of macropinocytosis in mammalian cell growth beyond Ras-transformed tumor cells via sustained mTORC1 activation.

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