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1.
Int Immunol ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38442194

RESUMO

The intestinal barrier consists of mucosal, epithelial, and immunological barriers and serves as a dynamic interface between the host and its environment. Disruption of the intestinal barrier integrity is a leading cause of various gastrointestinal diseases, such as inflammatory bowel disease. The homeostasis of the intestinal barrier is tightly regulated by crosstalk between gut microbes and the immune system; however, the implication of the immune system on the imbalance of gut microbes that disrupts barrier integrity remains to be fully elucidated. An inhibitory immunoglobulin-like receptor, Allergin-1, is expressed on mast cells and dendritic cells and inhibits Toll-like receptor (TLR)-2 and TLR-4 signaling in these cells. Since TLRs are major sensors of microbiota and are involved in local epithelial homeostasis, we investigated the role of Allergin-1 in maintaining intestinal homeostasis. Allergin-1-deficient (Milr1-/-) mice exhibited more severe dextran sulfate sodium (DSS)-induced colitis than did wild-type (WT) mice. Milr1-/- mice showed an enhanced intestinal permeability than did WT mice even before DSS administration. Treatment of Milr1-/- mice with neomycin, but not ampicillin, restored intestinal barrier integrity. The 16S rRNA gene sequencing analysis demonstrated that Bifidobacterium pseudolongum was the dominant bacteria in Milr1-/- mice after treatment with ampicillin. Although the transfer of B. pseudolongum to germ-free WT mice had no effect on intestinal permeability, its transfer into ampicillin-treated WT mice enhanced intestinal permeability. These results demonstrated that Allergin-1 deficiency enhanced intestinal dysbiosis with expanded B. pseudolongum, which contributes to intestinal barrier dysfunction in collaboration with neomycin-sensitive and ampicillin-resistant microbiota.

2.
Clin Immunol ; 259: 109892, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38185269

RESUMO

Radioresistance and metastasis are critical issues in managing oral squamous cell carcinoma (OSCC). Although immune checkpoint inhibitors (ICIs) has been recommended to treat OSCC, lacking useful biomarkers limited their anti-cancer effectiveness. We found that guanylate binding protein 5 (GBP5) is upregulated in primary tumors and associates with radioresistance in OSCC. GBP5 expression causally associated with cellular radioresistance and migration ability in the OSCC cell variants. GBP5 upregulation was examined to be correlated with NF-κB activation and programmed cell death-ligand 1 (PD-L1) elevation in OSCC samples. GBP5 knockdown was mitigated, but overexpression enhanced, NF-κB activity and PD-L1 expression in the OSCC cells. NF-κB inhibition by SN50 dramatically suppressed the GBP5-forested irradiation resistance, cellular migration ability and PD-L1 expression in OSCC cells. Importantly, GBP5 upregulation predicted a favorable outcome in cancer patients received ICI treatment. Our findings provide GBP5 as a useful biomarker to predict the anti-OSCC effectiveness of irradiation and ICIs.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Antígeno B7-H1 , Biomarcadores , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/genética , NF-kappa B , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
4.
Medicine (Baltimore) ; 102(35): e34900, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37657042

RESUMO

BACKGROUND: The purpose of this study was to explore efficacy of locally injected tranexamic acid (TXA) at a concentration of 1 mg/mL for reduction perioperative bleeding and postoperative complications in subcutaneous tumor excisions. We present the protocol and also compare results between the group of use antithrombotic group and not used. METHODS: This is a retrospective study. Fifty-three patients were divided into 3 groups. Group 1 (n = 14): using antithrombotic drugs (antiplatelet or anticoagulants) with locally injected TXA. Group 2 (n = 17): using antithrombotic drugs without locally injected TXA. Group 3 (n = 22): not using antithrombotic drugs but with locally injected TXA. TXA was diluted to 1 mg/mL for use based on our experience. All patients were operated by 1 surgeon in 1 single medical center in Taipei from March 1st, 2020, to March 31st 2022. Outcomes such as the quality of perioperative surgical field and postoperative surgical complications were evaluated and compared. The quality of field was intraoperatively recorded by an assessment and photos from the surgeon. The statistical relationships between the complication rates were analyzed using χ2 test and a 1-way ANOVA by SPSS 25. RESULTS: From Groups 1 and 3, a total of 36 patients, 29 patients had a clear surgical field during procedure. When comparing Groups 1 and 2, use of locally injected TXA had greater positive advantage in terms of a clearer vision whilst surgery (P = .031). Group 2 had more minor complications such as hematoma, severe ecchymosis, wound dehiscence, wound infection. By postoperatively reducing hematomas for 24 hours, it significantly reduce the incidence of abovementioned minor complications (P = .036). With the help of locally injected TXA, shorter time was required to remove drain, hence reducing duration of in-hospital stay. CONCLUSION: The use of locally injected TXA whilst performing subcutaneous surgery on patients taking antithrombotic drugs is cost-effective. It could reduce bleeding and provide a more effective surgical field. In our study, favorable results were obtained from the use of diluted tranexamic acid (1 mg/mL) mixed with lidocaine, namely in clearing the surgical field as well as reducing postoperative surgical complications.


Assuntos
Cirurgiões , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Fibrinolíticos , Estudos Retrospectivos , Complicações Pós-Operatórias/prevenção & controle , Hematoma
5.
Neurotoxicology ; 98: 9-15, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37429421

RESUMO

OBJECTIVE: Activity or expression of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) is diminished in some disease states such as cardiac failure and diabetes mellitus. A newly developed activator of SERCA, CDN1163, reportedly rescued or alleviated pathological conditions attributed to dysfunctional SERCA. We examined whether CDN1163 could relieve mouse neuronal N2A cell growth inhibition caused by cyclopiazonic acid (CPA, SERCA inhibitor). We also examined how CDN1163 affected cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential. METHODS: Cell viability was measured by MTT assay and trypan blue exclusion test. Cytosolic Ca2+, mitochondrial Ca2+ and mitochondrial membrane potential were measured using fura 2, Rhod-2 and JC-1, respectively, as fluorescent probes. RESULTS: CDN1163 (10 µM) itself suppressed cell proliferation, and did not alleviate CPA's inhibitory effect (and vice versa). Cell cycle was arrested at the G1 phase after CDN1163 treatment. CDN1163 treatment caused a slow yet persistent cytosolic [Ca2+] elevation partly due to Ca2+ release from an internal store other than the CPA-sensitive endoplasmic reticulum (ER). Treatment with CDN1163 for 3 h raised mitochondrial Ca2+ level and such increase was suppressed by MCU-i4 (an inhibitor of mitochondria Ca2+ uniporter, MCU), suggesting Ca2+ entered the mitochondrial matrix through MCU. Treatment of cells with CDN1163 up to 2 days resulted in mitochondrial hyperpolarization. CONCLUSION: CDN1163 caused internal Ca2+ leak, cytosolic Ca2+ overload, mitochondrial Ca2+ elevation and hyperpolarization, cell cycle arrest and cell growth inhibition.


Assuntos
Retículo Endoplasmático , Mitocôndrias , Camundongos , Animais , Mitocôndrias/metabolismo , Retículo Endoplasmático/metabolismo , Aminoquinolinas/metabolismo , Aminoquinolinas/farmacologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Pontos de Checagem do Ciclo Celular , Cálcio/metabolismo
6.
J Surg Case Rep ; 2023(7): rjad399, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37457861

RESUMO

Flexor pollicis longus (FPL) tendon rupture is a debilitating condition that can impair hand function. This case series study aimed to evaluate the outcomes of FPL tendon rupture and subsequent palmaris longus (PL) tendon graft reconstruction. Three cases of FPL tendon rupture in patients who had previously undergone open reduction and internal fixation with a volar plate were included. The surgical intervention involved volar plate removal, tenolysis and PL tendon graft reconstruction. Follow-up assessments showed gradual improvement in wrist function, with no post-operative complications or infections observed. These findings suggest that PL tendon grafting can be an effective surgical technique for FPL tendon rupture. Further research is needed to determine optimal surgical approaches and post-operative rehabilitation protocols for this condition.

7.
Nat Commun ; 14(1): 3666, 2023 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-37380635

RESUMO

Green leaf volatiles (GLVs) are short-chain oxylipins that are emitted from plants in response to stress. Previous studies have shown that oral secretions (OS) of the tobacco hornworm Manduca sexta, introduced into plant wounds during feeding, catalyze the re-arrangement of GLVs from Z-3- to E-2-isomers. This change in the volatile signal however is bittersweet for the insect as it can be used by their natural enemies, as a prey location cue. Here we show that (3Z):(2E)-hexenal isomerase (Hi-1) in M. sexta's OS catalyzes the conversion of the GLV Z-3-hexenal to E-2-hexenal. Hi-1 mutants that were raised on a GLV-free diet showed developmental disorders, indicating that Hi-1 also metabolizes other substrates important for the insect's development. Phylogenetic analysis placed Hi-1 within the GMCß-subfamily and showed that Hi-1 homologs from other lepidopterans could catalyze similar reactions. Our results indicate that Hi-1 not only modulates the plant's GLV-bouquet but also functions in insect development.


Assuntos
Líquidos Corporais , Manduca , Animais , Filogenia , Catálise , Folhas de Planta
9.
Ann Plast Surg ; 90(1 Suppl 1): S103-S110, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-37075300

RESUMO

BACKGROUND: As we all know, the numbers of aesthetic surgery are increasing around the world. After the surgery, the scar would be a problematic issue for both the surgeons and the patients. Silicone has proven to be effective for keloids, hypertrophic scars, and prevention of scar formation in many literatures for a long time. In terms of scar prevention, silicone has been used in the form of silicone sheets in early times, which is later improved to be the form of silicone gel with the advantage of easier usage. Although silicone gel has improved greatly in the aspect of appearance and convenience of the silicone sheets, there are still some disadvantages of the gel form. Therefore, the LeniScar silicone stick (AnsCare) is invented. OBJECTIVE: This article aimed to compare the results of scar treatment and prevention of the AnsCare LeniScar Silicone Stick versus the traditional silicone gel (Dermatix Ultra). METHODS: This study was a prospective, nonblinded, randomized clinical study. There were a total of 68 patients from September 2018 to January 2020. Patients were divided into 2 groups with AnsCare (n = 43) and Dermatix (n = 25), who both were required to schedule regular outpatient clinic follow-up, and photographs were taken before use, 1, 2, and 3 months later after the usage for the record. The physician assessed the scar condition by the Vancouver Scar Scale (VSS). The scores of the VSS were further analyzed and compared. RESULTS: The overall P value of total score of VSS was 0.635, which indicates that there is no significant difference in using AnsCare LeniScar Silicone Stick versus Dermatix Ultra silicone gel in terms of scar prevention and treatment. Individual items of VSS such as pliability, height, vascularity, and pigmentation all show no significant statistical difference in the 2 treatment products, with P = 0.980, 0.778, 0.528, and 0.366, respectively. CONCLUSION: Traditional Dermatix Ultra silicone gel has been effective in the treatment of scar formation. AnsCare LeniScar Silicone Stick is statistically not different from the Dermatix Ultra silicone gel when comparing the treatment results of scar prevention. Furthermore, the AnsCare LeniScar Silicone Stick has the advantages of being time-saving with no need to wait for it to dry and application of precise amount to precise location, preventing waste or overuse.


Assuntos
Cicatriz Hipertrófica , Queloide , Humanos , Géis de Silicone/uso terapêutico , Estudos Prospectivos , Cicatriz Hipertrófica/etiologia , Cicatriz Hipertrófica/prevenção & controle , Queloide/etiologia , Queloide/prevenção & controle , Resultado do Tratamento
10.
Insect Biochem Mol Biol ; 155: 103932, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36921734

RESUMO

Bumblebees (Bombus eximius) are one of the most prominent pollinators in the agricultural industry because of their adaptation to temperate climates and pollination behavior (buzz pollination). Several studies have explained the need to increase conservation efforts for bumblebees due to climate change, but studies on the impact of climate change on pollination behavior of bumblebees have been limited. The present study investigated the effect of elevated temperatures on the survival and physiology of bumblebees. The behavioral changes in flight ability and pollen collection were also determined. We found that elevated temperature affects the survival rate and appetite of bumblebees. Gene expression analysis suggested that the energy metabolic pathway tends to involve anaerobic respiration during heat stress. The energy produced is mainly used to maintain essential physiological functions, such as expression of heat shock proteins and conversion of peroxides to harmless molecules. Energy distributed to flight muscles is reduced during heat stress, resulting in lower wing beating frequency. In addition, the flight path of bumblebees is shortened during heat stress, thereby further contributing to reduced pollen collection. These results demonstrate that elevated temperatures cause detrimental effects to bumblebees and can also potentially reduce crop production.


Assuntos
Metabolismo Energético , Polinização , Abelhas/genética , Animais , Temperatura , Comportamento Animal , Pólen
11.
J Clin Med ; 12(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36675407

RESUMO

The relationship between quantitative anatomic parameters in MRI and patient-reported outcomes (PROs) before and after surgery in degenerative lumbar foraminal stenosis remains unknown. We included 58 patients who underwent transforaminal lumbar interbody fusion (TLIF) for single-level degenerative disc disease with foraminal stenosis between February 2013 and June 2020. PROs were evaluated using the visual analog scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). The foraminal parameters assessed using preoperative MRI included foraminal height, posterior intervertebral disc height, superior and inferior foraminal width, and foraminal area. The correlation between foraminal parameters and PROs before operation, at 1 year follow-up, and change from baseline were assessed. The associations between the aforementioned parameters were examined using linear regression analysis. The analysis revealed that among these parameters, superior foraminal width was found to be significantly correlated with ODI and EQ-5D at the 1 year follow-up and with change in ODI and EQ-5D from baseline. The associations remained significant after adjustment for confounding factors including age, sex, body mass index, and duration of hospital stay. The results indicated that in degenerative lumbar foraminal stenosis, decreased superior foraminal width was associated with better improvement in disability and quality of life after TLIF.

12.
Pest Manag Sci ; 79(2): 701-710, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36250989

RESUMO

BACKGROUND: Bio-pesticide development is an important area of research in agriculture, in which viruses are an essential tool. Infection by entomological pathogenic viruses kills agricultural pests, and viral progenies are disseminated to infect more pests, eventually achieving long-term pest control in the field. Of the current virus-based pest control models, Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the most studied. AcMNPV belongs to the Baculoviridae family and can infect many lepidopterans. Although AcMNPV has been previously demonstrated to be a potential pest-control tool, its long virus infection cycle has made field applications challenging. To overcome this, we generated a recombinant baculovirus that can express mammalian galectin-1, which is a galactoside-binding protein that binds to the peritrophic matrix in the midgut of lepidopteran pests and induces perforation of the membrane. RESULTS: Hosts infected with a recombinant virus that expressed mammalian galectin-1 exhibited reduced appetite and died sooner in both laboratory and small-scale field studies, suggesting that the overexpression of galectin-1 can more efficiently eliminate pest hosts. In addition to disrupting the integrity of the peritrophic matrix, the immune system of hosts infected with recombinant baculovirus carrying the galectin-1 gene was suppressed, making hosts more vulnerable to secondary infection. CONCLUSION: Galectin-1 has been shown to affect immune responses in mammals, including humans, but to our knowledge, the effect of galectin-1 on insect immune systems had not been previously reported. Our results demonstrated that the pest-control potential of baculoviruses can be improved by using a recombinant baculovirus that overexpresses mammalian galectin-1 in hosts. © 2022 Society of Chemical Industry.


Assuntos
Baculoviridae , Galectina 1 , Inseticidas , Animais , Baculoviridae/genética , Galectina 1/genética , Galectina 1/metabolismo , Inseticidas/farmacologia , Inseticidas/metabolismo , Mamíferos/genética , Spodoptera/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
13.
Front Med (Lausanne) ; 9: 1058636, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36479098

RESUMO

Purpose: We investigated the association between pre-operative anemia and long-term all-cause mortality in patients with vertebral fracture who underwent a vertebroplasty. Materials and methods: We retrospectively selected patients who were admitted for vertebroplasty for vertebral compression fracture between 2013 and 2020. Patients who had pathologic fractures or had no assessment of bone mineral density were excluded. Relevant information was collected from electronic medical records. Patients' survival status was confirmed at the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of anemia (<12 g/dL vs. ≥12 g/dL) and pre-operative hemoglobin levels (as a continuous variable) on all-cause mortality with multivariate adjustments. Results: A total of 167 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.7%). After a median follow-up duration of 2.1 years, pre-operative anemia (hemoglobin <12 g/dL vs. ≥12 g/dL) was independently associated with a higher risk of all-cause mortality (hazard ratio 2.762, 95% CI 1.184 to 6.442, p = 0.019). An increase in pre-operative hemoglobin was associated with a lower risk of all-cause mortality after multivariate adjustment (hazard ratio 0.775, 95% CI 0.606 to 0.991, p = 0.042). Conclusion: Pre-operative anemia (<12 g/dL) was independently associated with survival outcome among patients with vertebral compression fractures who underwent vertebroplasty. Our findings highlight anemia as a risk factor of long-term mortality in this elderly surgical population.

14.
J Clin Med ; 11(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36362747

RESUMO

We aimed to investigate the association between preoperative body mass index (BMI) and postoperative long-term mortality in patients who underwent a vertebroplasty. We retrospectively enrolled patients with a vertebral compression fracture who underwent a vertebroplasty between May 2013 and June 2020 in a medical center in Taiwan. The survival status of the study sample was confirmed by the end of March 2021. Cox-proportional hazard models were conducted to examine the effects of being overweight/obese (≥25 kg/m2 vs. <25 kg/m2) and BMI (as a continuous variable) on all-cause mortality after adjusting for age, sex, history of smoking, diabetes, hypertension, chronic kidney disease, and osteoporosis. A total of 164 patients were analyzed (mean age 75.8 ± 9.3 years, male 25.6%, mean BMI 24.0 ± 4.1 kg/m2) after a median follow-up of 785 days. Compared with a BMI < 25 kg/m2, a BMI ≥ 25 kg/m2 was associated with a significantly lower risk of all-cause mortality (HR 0.297, 95% CI 0.101 to 0.878, p = 0.028). These findings were consistent when BMI was examined as a continuous variable (HR 0.874, 95% CI 0.773 to 0.988, p = 0.031). A low BMI (<22 kg/m2) should be considered as a risk factor for postoperative long-term mortality in this ageing population.

15.
Front Surg ; 9: 911514, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061052

RESUMO

Oblique lumbar interbody fusion (OLIF) is a popular technique for the treatment of degenerative lumbar spinal disease. There are no clear guidelines on whether direct posterior decompression (PD) is necessary after OLIF. The purpose of this study was to analyze the effect of the indirect decompression obtained from OLIF in patients with lumbar foraminal stenosis. We retrospectively reviewed 33 patients who underwent OLIF surgery for degenerative lumbar spinal disease between 1 January 2018, and 30 June 2019. The inclusion criteria included patients who were diagnosed with lumbar foraminal stenosis by preoperative MRI. The exclusion criteria included the presence of central canal stenosis, spinal infection, vertebral fractures, and spinal malignancies. The clinical results, evaluated using the visual analogue scale of back pain (VAS-Back), VAS of leg pain (VAS-Leg), and Oswestry disability index (ODI), were recorded. The radiologic parameters were also measured. The VAS-Back, VAS-Leg, and ODI showed significant improvement in both the PD and non-posterior decompression (Non-PD) groups postoperatively (all, p < 0.05). Patients in the Non-PD group showed better results than those in the PD group in the VAS-Back at 12- and 24 months postoperatively (0.00 vs. 3.00 postoperatively at 12 months, p = 0.030; 0.00 vs. 4.00 postoperatively at 24 months, p = 0.009). In addition, the ODI at 24 months postoperatively showed better improvement in the Non-PD group (8.89 vs. 24.44, p = 0.038). The disc height in both the PD and the Non-PD groups increased significantly postoperatively (all, p < 0.05), but the restoration of foraminal height was significantly different only in the Non-PD group. There was no statistically significant difference in cage position, cage subsidence, fusion grade, or screw loosening between the PD and the Non-PD groups. Indirect decompression via OLIF for lumbar foraminal stenosis showed favorable outcomes. The use of interbody cages and posterior instrumentation was sufficient for relieving symptoms in patients with lumbar foraminal stenosis. Additional direct posterior decompression may deteriorate results in the follow-up period.

16.
J Clin Med ; 11(17)2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36078918

RESUMO

Robot-assisted pedicle screw placement for spine surgery has become popular in recent years. This study compares clinical, radiographic outcomes and the screw loosening rate between robot-assisted and fluoroscopy-guided pedicle screw placement in patients who underwent transforaminal lumbar interbody fusion (TLIF). We retrospectively examined 108 patients with the degenerative lumbar disease who underwent TLIF. According to whether the robotic system was used, patients were assigned to either the robot-assisted (Ro TLIF, n = 29) or fluoroscopy-guided TLIF (FG TLIF, n = 79) group. Radiographic parameters and patient-reported outcomes, including leg and back pain visual analog scale (VAS) and Oswestry Disability Index (ODI), were assessed. Loosening signs were noted in 48 out of 552 pedicle screws. The screw loosening rate was higher in the FG TLIF (10.2%) than Ro TLIF group (4.3%). A significant correlation was found between screw loosening and age, the number of level(s) fused, and the ratio of the average distance from the pedicle screw to the upper endplate to vertebral body height. VAS-leg, VAS-back, and ODI showed significant improvements in both groups postoperatively (all p < 0.05). These results indicated that robot-assisted pedicle screw placement in TLIF had a lower screw loosening rate and similar patient-reported outcomes compared with the fluoroscopy-guided technique.

17.
Front Cell Dev Biol ; 10: 945572, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105362

RESUMO

Concentrative nucleoside transporters (Cnts) are unidirectional carriers that mediate the energy-costly influx of nucleosides driven by the transmembrane sodium gradient. Cnts are transmembrane proteins that share a common structural organization and are found in all phyla. Although there have been studies on Cnts from a biochemical perspective, no deep research has examined their role at the organismal level. Here, we investigated the role of the Drosophila melanogaster cnt1 gene, which is specifically expressed in the testes. We used the CRISPR/Cas9 system to generate a mutation in the cnt1 gene. The cnt1 mutants exhibited defects in the duration of copulation and spermatid maturation, which significantly impaired male fertility. The most striking effect of the cnt1 mutation in spermatid maturation was an abnormal structure of the sperm tail, in which the formation of major and minor mitochondrial derivatives was disrupted. Our results demonstrate the importance of cnt1 in male fertility and suggest that the observed defects in mating behavior and spermatogenesis are due to alterations in nucleoside transport and associated metabolic pathways.

18.
EClinicalMedicine ; 51: 101497, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35844773

RESUMO

Background: Diabetic foot and leg ulcers are a major cause of disability among patients with diabetes mellitus. A topical gel called ENERGI-F703, applied twice daily and with adenine as its active pharmaceutical ingredient, accelerated wound healing in diabetic mice. The current study evaluated the safety and efficacy of ENERGI-F703 for patients with diabetic foot and leg ulcers. Methods: This randomized, double-blind, multicenter, phase II trial recruited patients from eight medical centers in Taiwan. Patients with intractable diabetic foot and leg ulcers (Wagner Grade 1-3 without active osteomyelitis) were randomly assigned (2:1) to receive topical ENERGI-F703 gel or vehicle gel twice daily for 12 weeks or until complete ulcer closure. The investigator, enrolled patients and site personnel were masked to treatment allocation. Intention to treat (ITT) population and safety population were patient to primary analyses and safety analyses, respectively. Primary outcome was complete ulcer closure rate at the end of treatment. This trial is registered with ClinicalTrials.gov, number NCT02672436. Findings: Starting from March 15th, 2017 to December 26th, 2019, 141 patients were enrolled as safety population and randomized into ENERGI-F703 gel (n = 95) group or vehicle gel (n = 46) group. In ITT population, ENERGI-F703 (n = 90) and vehicle group showed ulcer closure rates of 36.7% (95% CI = 26.75% - 47.49%) and 26.2% (95% CI = 13.86% - 42.04%) with difference of 9.74 % (95 % CI = -6.74% - 26.23%) and 25% quartiles of the time to complete ulcer closure of 69 days and 84 days, respectively. There were 25 (26.3%) patients in ENERGI-F703 group and 11 (23.9%) patients in vehicle group experiencing serious adverse events and five deaths occurred during the study period, none of them related to the treatment. Interpretation: Our study suggests that ENERGI-F703 gel is a safe and well-tolerated treatment for chronic diabetic foot and leg ulcers. Further studies are needed to corroborate our findings in light of limitations. Funding: Energenesis Biomedical Co., Ltd.

19.
Front Surg ; 9: 853441, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35372486

RESUMO

Aim: Limited data are available on the impact of the coronavirus disease 2019 (COVID-19) pandemic on patient-reported outcome measures (PROMs) in patients who underwent spine surgery. In this study, we aimed to investigate the associations between the COVID-19 outbreak in Taiwan (May 2021) and PROMs in patients who underwent spine surgery. Method: We retrospectively identified patients who underwent spine surgery during identical defined 6-week time-intervals (May 16 to June 30) in 2019, 2020, and 2021. PROMs, including visual analog scale (VAS) score for pain, Oswestry disability index (ODI), and EuroQol-5D (EQ-5D), were investigated before surgical intervention and at a 1-month follow-up. Relevant clinical information was collected from the electronic medical records of patients. Linear regression analysis was used to examine the association between the pandemic in 2021 (vs. 2019/2020) and the PROMs after adjusting for age, sex, and relevant clinical variables. Results: The number of patients who underwent spine surgery at our hospital during the identical defined 6-week time-intervals in 2019, 2020, and 2021 was 77, 70, and 48, respectively. The surgical intervention significantly improved VAS, ODI, and EQ-5D of the patients (1 month after surgery vs. before surgery, all p < 0.001) in all three study periods. However, there was a significant between-group difference in change from baseline in VAS (p = 0.002) and EQ-5D (p = 0.010). The decrease in VAS and increase in EQ-5D after surgery in 2021 were not as much as those in 2019 and 2020. The associations between the pandemic in 2021 (vs. 2019/2020) and changes in VAS (ß coefficient 1.239; 95% confidence interval [CI] 0.355 to 2.124; p = 0.006) and EQ-5D (ß coefficient, -0.095; 95% CI, -0.155 to -0.035; p = 0.002) after spine surgery were independent of relevant clinical factors. Conclusion: There was less improvement in short-term PROMs (VAS and EQ-5D) after spine surgery during the COVID-19 pandemic. Assessment of PROMs in surgical patients during a pandemic may be clinically relevant, and psychological support in this condition might help improve patients' outcomes.

20.
Insect Biochem Mol Biol ; 139: 103674, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34737063

RESUMO

Deformed wing virus (DWV) infection is believed to be closely associated with colony losses of honeybee (Apis mellifera) due to reduced learning and memory of infected bees. The adenosine (Ado) pathway is important for maintaining immunity and memory function in animals, and it enhances antivirus responses by regulating carbohydrate metabolism in insects. Nevertheless, its effect on the memory of invertebrates is not yet clear. This study investigated how the Ado pathway regulates energy metabolism and memory in honeybees following DWV infection. Decreased Ado receptor (Ado-R) expression in the brain of infected bees resulted in a carbohydrate imbalance as well as impairments of glutamate-glutamine (Glu-Gln) cycle and long-term memory. Dietary supplementation with Ado not only increased the brain energy metabolism but also rescued long-term memory loss by upregulating the expression of memory-related genes. The present study demonstrated the regulation of the Ado pathway upon DWV infection and provides insights into the mechanisms underlying energy regulation and the neurological function of honeybees.


Assuntos
Adenosina/metabolismo , Abelhas/virologia , Vírus de RNA/fisiologia , Transdução de Sinais , Animais , Metabolismo Energético , Memória
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