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1.
Artigo em Inglês | MEDLINE | ID: mdl-35549565

RESUMO

Fretting corrosion as one of the leading causes for failure of modular hip prostheses has been associated with micromotion at head-neck taper junction. Decomposition of micromotion is helpful to promote the development of more realistic experiments investigating failure mechanisms of the head-neck junction in total hip arthroplasty. The aim of this study was to decompose the complex three-dimensional micromotion at the head-neck junction into multiple fundamental modes, including three translational and three rotational components. A three-dimensional finite element model composed of head-neck junction, liner and acetabular cup with a typical 12/14 taper size, as well as the taper mismatch of -4', was developed during walking. The analysis was divided into three procedures: a) the assembly simulation of the head and neck during surgery, b) verification with a simplified axisymmetric model, and c) three-dimensional modelling under normal walking. This study revealed that the main forms of micromotion contained circumferential, longitudinal micromotion and longitudinal rolling toggling, and were closely related to the state of motion. The maximum translational micromotion was predicted to be 10.9 µm during the walking gait, with the predominant modes of the circumferential translation of 9.6 µm, the longitudinal translation of 5.5 µm and the longitudinal rotation of 0.29° along the taper junction. These findings may provide design considerations for further experimental testing about fretting and facilitate the understanding of the fretting mechanisms in hip prostheses.

2.
mBio ; : e0372121, 2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35491828

RESUMO

The rhizobium-legume symbiosis is essential for sustainable agriculture by reducing nitrogen fertilizer input, but its efficiency varies under fluctuating soil conditions and resources. The nitrogen-related phosphotransferase system (PTSNtr) consisting of PtsP, PtsO, and PtsN is required for optimal nodulation and nitrogen fixation efficiency of the broad-host-range Sinorhizobium fredii CCBAU45436 associated with diverse legumes, though the underlying mechanisms remain elusive. This work characterizes the PtsN-KdpDE-KdpFABC pathway that contributes to low potassium adaptation and competitive nodulation of CCBAU45436. Among three PtsN, PtsN1 is the major functional homolog. The unphosphorylated PtsN1 binds the sensory kinase KdpD through a non-canonical interaction with the GAF domain of KdpD, while the region covering HisKA-HATPase domains mediates the interaction of KdpD with the response regulator KdpE. KdpE directly activates the kdpFABC operon encoding the conserved high-affinity potassium uptake system. Disruption of this signaling pathway leads to reduced nodule number, nodule occupancy, and low potassium adaptation ability, but without notable effects on rhizoplane colonization. The induction of key nodulation genes NIN and ENOD40 in host roots during early symbiotic interactions is impaired when inoculating the kdpBC mutant that shows delayed nodulation. The nodulation defect of the kdpBC mutant can be rescued by supplying replete potassium. Potassium is actively consumed by both prokaryotes and eukaryotes, and components of the PTSNtr-KdpDE-KdpFABC pathway are widely conserved in bacteria, highlighting the global importance of this pathway in bacteria-host interactions. IMPORTANCE In all ecological niches, potassium is actively consumed by diverse prokaryotes and their interacting eukaryote hosts. It is only just emerging that potassium is a key player in host-pathogen interactions, and the role of potassium in mutualistic interactions remains largely unknown. This work is focused on the mutualistic symbiosis between rhizobia and legumes. We report that the nitrogen-related phosphotransferase system PTSNtr, the two-component system KdpDE, and the high-affinity potassium uptake system KdpFABC constitute a pathway that is important for low potassium adaptation and optimal nodulation of rhizobia. Given the widely conserved PTSNtr, KdpDE, and KdpFABC in bacteria and increasing knowledge on microbiome for various niches, the PTSNtr-KdpDE-KdpFABC pathway can be globally important in the biosphere.

3.
Front Cardiovasc Med ; 9: 864188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35509278

RESUMO

Thoracic radiotherapy patients have higher risks of developing radiation-induced heart disease (RIHD). Ionizing radiation generates excessive reactive oxygens species (ROS) causing oxidative stress, while Momordica. charantia and its extract have antioxidant activity. Plant-derived extracellular vesicles (EVs) is emerging as novel therapeutic agent. Therefore, we explored the protective effects of Momordica. charantia-derived EVs-like nanovesicles (MCELNs) against RIHD. Using density gradient centrifugation, we successfully isolated MCELNs with similar shape, size, and markers as EVs. Confocal imaging revealed that rat cardiomyocytes H9C2 cells internalized PKH67 labeled MCELNs time-dependently. In vitro assay identified that MCELNs promoted cell proliferation, suppressed cell apoptosis, and alleviated the DNA damage in irradiated (16 Gy, X-ray) H9C2 cells. Moreover, elevated mitochondria ROS in irradiated H9C2 cells were scavenged by MCELNs, protecting mitochondria function with re-balanced mitochondria membrane potential. Furthermore, the phosphorylation of ROS-related proteins was recovered with increased ratios of p-AKT/AKT and p-ERK/ERK in MCELNs treated irradiated H9C2 cells. Last, intraperitoneal administration of MCELNs mitigated myocardial injury and fibrosis in a thoracic radiation mice model. Our data demonstrated the potential protective effects of MCELNs against RIHD. The MCELNs shed light on preventive regime development for radiation-related toxicity.

4.
Curr Med Sci ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451807

RESUMO

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a common cause of clinical liver dysfunction and an important prepathological change of liver cirrhosis. Central obesity, type 2 diabetes mellitus, dyslipidemia, and metabolic syndrome are the major risk factors for NAFLD. Sitagliptin (Sig) is a novel hypoglycemic agent that improves blood glucose levels by increasing the level of active incretin. Sig has been shown to prevent the development of fatty livers in mice on a fructose-rich diet. The purpose of this study was to observe the efficacy of Sig on NAFLD in type 2 diabetic mice. METHODS: The diet-induced obesity mouse model was established, and the diabetic mice were screened by an intraperitoneal glucose tolerance trial. The mice were randomly divided into four groups for 8 weeks of intervention: high-fat diet (HFD) group, Sig group, metformin (Met) group, and Sig+Met group. After the intervention, the liver function indexes as well as the blood glucose and blood lipid levels of the mice were measured. In addition, the wet weight of the liver was measured; the pathological sections of the liver tissues were stained to observe the hepatocyte fatty degeneration, inflammation, necrosis, and fibrosis; and the hepatic histological injury was recorded as the NAFLD activity score (NAS). RESULTS: Compared with the normal control group, the body weight, liver weight, blood glucose level, insulin resistance (IR), blood lipid level, and transaminase level of the mice in the HFD group were significantly increased, showing typical metabolic syndrome. After treatment with Sig and/or Met, the mice gained less weight, had lower levels of blood glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and transaminase, and had improved IR compared with the HFD group. The liver pathological NASs in the Sig group (P=0.01), Met group (P=0.028), and Sig+Met group (P<0.001) were lower than those in the HFD group (P<0.05), suggesting that the use of the two drugs alone or in combination can improve the state of liver inflammation. In terms of fibrosis, there was no fibrosis in the control group but there was significant fibrosis in the HFD group (P<0.001). There was no significant difference between the drug intervention groups and the HFD group, indicating that the drug therapy (Sig and/or Met) did not significantly improve the pre-existing fibrosis. CONCLUSION: Our experiment proved that Sig can improve NAFLD, including improvement of the serum transaminase level, hepatic pathological inflammation level, and hepatocyte adiposis, suggesting that Sig may play a role by improving glucose and lipid metabolism, reducing the body weight and liver weight, improving insulin sensitivity, and inhibiting fatty liver inflammation. Sig may be a new direction for the treatment of patients with a nonalcoholic fatty liver and diabetes, delaying the progression of NAFLD.

5.
Comput Struct Biotechnol J ; 20: 1642-1653, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465163

RESUMO

Gefapixant/AF-219, a selective inhibitor of the P2X3 receptor, is the first new drug other than dextromethorphan to be approved for the treatment of refractory chronic cough (RCC) in nearly 60 years. To date, seven P2X subtypes (P2X1-7) activated by extracellular ATP have been cloned, and subtype selectivity of P2X inhibitors is a prerequisite for reducing side effects. We previously identified the site and mechanism of action of Gefapixant/AF-219 on the P2X3 receptor, which occupies a pocket consisting of the left flipper (LF) and lower body (LB) domains. However, the mechanism by which AF-219 selectively acts on the P2X3 receptor is unknown. Here, we combined mutagenesis, chimera construction, molecular simulations, covalent occupation and chemical synthesis, and find that the negative allosteric site of AF-219 at P2X3 is also present in other P2X subtypes, at least for P2X1, P2X2 and P2X4. By constructing each chimera of AF-219 sensitive P2X3 and insensitive P2X2 subtypes, the insensitive P2X2 subtype was made to acquire the inhibitory properties of AF-219 and AF-353, an analog of AF-219 with higher affinity. Our results suggest that the selectivity of AF-219/AF-353 for P2X3 over the other P2X subtypes is determined by a combination of the accessibility of P2X3 binding site and the internal shape of this pocket, a finding that could provide new perspectives for drug design against P2X3-mediated diseases such as RCC, idiopathic pulmonary fibrosis, hypertension and overactive bladder disorder.

6.
Insect Sci ; 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35446483

RESUMO

The circadian clock plays a critical role in the regulation of host immune defense. However, the mechanistic basis for this regulation is largely unknown. Herein, the core clock gene cryptochrome1 (cry1) knockout line in Bombyx mori, an invertebrate animal model, was constructed to obtain the silkworm with dysfunctional molecular clock, and the dynamic regulation of the circadian clock on the immune responsiveness within 24 h of Staphylococcus aureus infection was analyzed. We found that deletion of cry1 decreased viability of silkworms and significantly reduced resistance of larvae to S. aureus. Time series RNA-seq analysis identified thousands of rhythmically expressed genes, including immune response genes, in the larval immune tissue, fat bodies. Uninfected cry1 knockout silkworms exhibited expression patterns of rhythmically expressed genes similar to wild-type (WT) silkworms infected with S. aureus. However, cry1 knockout silkworms exhibited a seriously weakened response to S. aureus infection. The immune response peaked at 6 and 24 h after infection, during which "transcription storms" occurred, and the expression levels of the immune response genes, PGRP and antimicrobial peptides (AMPs), were significantly upregulated in WT. In contrast, cry1 knockout did not effectively activate Toll, Imd, or NF-κB signaling pathways during the immune adjustment period from 12 to 18 h after infection, resulting in failure to initiate the immune responsiveness peak at 24 h after infection. This may be related to inhibited silkworm fat body energy metabolism. These results demonstrated the dynamic regulation of circadian clock on silkworm immune response to bacterial infection and provided important insights into host antimicrobial defense mechanisms.

7.
Cell Biosci ; 12(1): 44, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35428322

RESUMO

BACKGROUND: The Ilheus virus (ILHV) is an encephalitis associated arthropod-borne flavivirus. It was first identified in Ilheus City in the northeast Brazil before spreading to a wider geographic range. No specific vaccines or drugs are currently available for the treatment of ILHV infections. The ILHV helicase, like other flavivirus helicases, possesses 5'-triphosphatase activity. This allows it to perform ATP hydrolysis to generate energy as well as sustain double-stranded RNA's unwinding during ILHV genome replication. Thus, ILHV helicase is an ideal target for inhibitor design. RESULTS: We determined the crystal structure of the ILHV helicase at 1.75-Å resolution. We then conducted molecular docking of ATP-Mn2+ to the ILHV helicase. Comparisons with related flavivirus helicases indicated that both the NTP and the RNA-ILHV helicase binding sites were conserved across intra-genus species. This suggested that ILHV helicase adopts an identical mode in recognizing ATP/Mn2+. However, the P-loop in the active site showed a distinctive conformation; reflecting a different local structural rearrangement. ILHV helicase enzymatic activity was also characterized. This was found to be relatively lower than that of the DENV, ZIKV, MVE, and ALSV helicases. Our structure-guided mutagenesis revealed that R26A, E110A, and Q280A greatly reduced the ATPase activities. Moreover, we docked two small molecule inhibitors of DENV helicase (ST-610 and suramin) to the ILHV helicase and found that these two molecules had the potential to inhibit the activity of ILHV helicase as well. CONCLUSION: High-resolution ILHV helicase structural analysis demonstrates the key amino acids of ATPase activities and could be useful for the design of inhibitors targeting the helicase of ILHV.

8.
Front Microbiol ; 13: 872550, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444630

RESUMO

The number of co-infections with multiple porcine diarrhea viruses has increased in recent years. Inducing mucosal immunity through oral immunization is an effective approach for controlling these pathogens. To generate a multi-pathogen vaccine against viral co-infection, we employed the Lactobacillus vector platform, which was previously used to generate potent candidate vaccines against various diseases. Two strategies were used to test the protective efficiency of recombinant Lactobacillus against multiple diarrhea viruses. First, we used a mixture of recombinant Lactobacillus separately expressing antigens of transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine rotavirus (PoRV). Next, we used a recombinant Lactobacillus expressing an antigen fusion protein of the above viruses. Twenty-four newborn piglets were divided into three groups and orally immunized with a mixture of recombinant Lactobacillus, recombinant Lactobacillus expressing the antigen fusion protein, or sterile phosphate-buffered saline daily for seven consecutive days after birth. After immunization, the piglets were randomly selected from each group for oral administration of PEDV, and these piglets were then cohabited with piglets without PEDV infection for 7 days. The protective effect against PEDV was evaluated based on clinical symptoms, viral shedding, and intestinal pathological damage. Piglets immunized with recombinant Lactobacillus showed specific mucosal and humoral immune responses to the three viruses and were protected against severe diarrhea and intestinal pathology. Our results highlight the potential of an oral multi-pathogen vaccine based on Lactobacillus to prevent transmission and limit the severity of viral co-infection.

9.
Biochem Biophys Res Commun ; 609: 84-92, 2022 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-35421633

RESUMO

Autophagy is a double-edged sword that affects tumor progression by promoting cell survival or death depending on different living contexts. The concrete mechanism by which autophagy modulates the efficacy of radiotherapy for prostate cancer (PC) remains unclear. We exposed RM-1 PC cells to X-ray and explored the role of autophagy in radiation injury. Our results showed increased apoptosis and autophagy levels in RM-1 cells after radiation. Pharmacological inhibition of autophagy by chloroquine significantly mitigated radiation-induced apoptosis, while the enhancement of autophagy by rapamycin aggravated apoptosis. Sirt1, a member of sirtuin family, deacetylates various transcription factors to trigger cell survival in response to radiation injury. We found that radiation led to Sirt1 downregulation, which was reversed by the inhibition of autophagy. On the contrary, enhanced autophagy further diminished protein level of Sirt1. Notably, overexpression of Sirt1 by plasmid significantly alleviated radiation-induced apoptosis, but silenced Sirt1 by siRNA further induced apoptosis, indicating the radioprotective effect of Sirt1 on RM-1 cells. In summary, our findings suggested that autophagy-mediated Sirt1 downregulation might be a promising therapeutic target for PC.


Assuntos
Neoplasias da Próstata , Lesões por Radiação , Sirtuína 1/metabolismo , Animais , Apoptose , Autofagia , Regulação para Baixo , Humanos , Masculino , Camundongos , Neoplasias da Próstata/genética , Neoplasias da Próstata/radioterapia , Tolerância a Radiação , Sirtuína 1/genética
10.
Front Immunol ; 13: 854995, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359966

RESUMO

Tumor necrosis factor (TNF)-like cytokine 1A (TL1A), a member of the TNF family, exists in the form of membrane-bound (mTL1A) and soluble protein (sTL1A). TL1A binding its only known functional receptor death domain receptor 3 (DR3) affects the transmission of various signals. This study first proposed that the TL1A/DR3 axis was significantly upregulated in patients and mice with both asthma and high TNF-a expression and in TNF-a-stimulated epithelial Beas-2B cells. Two independent approaches were used to demonstrate that the TL1A/DR3 axis of mice was strongly correlated with TNF-a in terms of exacerbating asthmatic epithelial-mesenchymal transformation (EMT). First, high expression levels of EMT proteins (e.g., collagen I, fibronectin, N-cadherin, and vimentin) and TL1A/DR3 axis were observed when mice airways were stimulated by recombinant mouse TNF-a protein. Moreover, EMT protein and TL1A/DR3 axis expression synchronously decreased after mice with OVA-induced asthma were treated with infliximab by neutralizing TNF-a activity. Furthermore, the OVA-induced EMT of asthmatic mice was remarkably improved upon the deletion of the TL1A/DR3 axis by knocking out the TL1A gene. TL1A siRNA remarkably intervened EMT formation induced by TNF-a in the Beas-2B cells. In addition, EMT was induced by the addition of high concentrations of recombinant human sTL1A with the cell medium. The TL1A overexpression via pc-mTL1A in vitro remarkably increased the EMT formation induced by TNF-a. Overall, these findings indicate that the TL1A/DR3 axis may have a therapeutic role for asthmatic with high TNF-a level.


Assuntos
Asma , Membro 25 de Receptores de Fatores de Necrose Tumoral , Animais , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Camundongos , Ovalbumina , Membro 25 de Receptores de Fatores de Necrose Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo
11.
Clin Biomech (Bristol, Avon) ; 94: 105633, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35364404

RESUMO

BACKGROUND: Tribocorrosion at head-neck interface is one of the main causes leading to the failure of hip implants in total hip arthroplasty. Impaction load has been acknowledged as one of the key factors influencing the stability of the taper junction. It is understood that the magnitude of impaction force differs from the surgeon to surgeon in primary total hip arthroplasty or revision. Clinically, it is sufficient enough to keep the male and female tapers inseparable utilizing a low impaction, which seems to contradict previous researches. The objective of this study was to investigate the effect of impaction loads on the stability of taper junction during assembly and gaits. METHODS: A finite element model with 12/14 taper and the taper mismatch of 4' was developed for investigation. The impaction force profiles were collected from surgeon as the inputs, and then the contact mechanics over one or multiple gaits was further analyzed and validated utilizing hip simulator test. FINDINGS: Impaction force ranging from 200 to 2000 N could provide the same taper connection effect after the first gait due to the secondary seating. As for impaction loads of 3000 N and above, an increased impaction force would lead to the tighter taper connection. INTERPRETATION: The effect of impaction load on the stability of head-neck junction is a piecewise function, indicating that the stability of taper junction is not affected by different impaction loads and tends to be consistent while its magnitude is below the threshold. Instead, the stability of taper junction is positively correlated with impaction force.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Feminino , Cabeça , Humanos , Masculino , Fenômenos Mecânicos , Desenho de Prótese
12.
Biomed Environ Sci ; 35(4): 296-311, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35473894

RESUMO

Objective: The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate (DHA-Na) and to determine the point of departure (POD), which is a critical factor in the establishment of an acceptable dietary intake. Methods: DHA-Na was administered once daily by gavage to Sprague-Dawley rats at dose levels of 0.0, 31.0, 62.0, and 124.0 mg/kg BW per day for 90 days, followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups. The outcome parameters were mortality, clinical observations, body weights, food consumption, hematology and clinical biochemistry, endocrine hormone levels, and ophthalmic, urinary, and histopathologic indicators. The benchmark dose (BMD) approach was applied to estimate the POD. Results: Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate, whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group. Importantly, the 95% lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight. Conclusion: The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels (62.0 and 124.0 mg/kg BW) after a 90-day oral exposure.


Assuntos
Pironas , Animais , Peso Corporal , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley
13.
Viruses ; 14(3)2022 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-35337027

RESUMO

The primary aim of this study was to evaluate the efficacy of phage against mastitis induced by drug-resistant S. aureus in a mouse model. In this study, five S. aureus phages-4086-1, 4086-2, 4086-3, 4086-4, and 4086-6-were isolated from milk samples secreted by mastitis cows. Transmission electron microscopy showed that all the five phages had icosahedral heads and short non-contractile tails, which are typical characteristics of the family Podoviridae. All these phages were species-specific against S. aureus. The one-step growth curve showed a short latency period (10-20 min) and high burst size (up to 400 PFU/infected cell). To evaluate the effectiveness of the phage 4086-1 in the treatment against mastitis, a mouse model of mastitis was challenged with drug-resistant S. aureus. The results showed the proliferation of S. aureus in the mammary glands was significantly inhibited after treating by phage 4086-1. The concentrations of TNF-α and IL-6 decreased significantly, which demonstrated the phages could effectively alleviate the inflammatory responses. Furthermore, the histopathological analysis showed that inflammatory infiltration in the mammary glands was significantly reduced. These results demonstrate that phage may be a promising alternative therapy against mastitis caused by drug-resistant S. aureus.


Assuntos
Bacteriófagos , Mastite Bovina , Staphylococcus aureus Resistente à Meticilina , Terapia por Fagos , Infecções Estafilocócicas , Animais , Bovinos , Feminino , Humanos , Mastite Bovina/terapia , Camundongos , Myoviridae , Terapia por Fagos/métodos , Infecções Estafilocócicas/terapia , Staphylococcus aureus
14.
Nat Commun ; 13(1): 1608, 2022 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-35338130

RESUMO

Cytoplasmic incompatibility (CI) results when Wolbachia bacteria-infected male insects mate with uninfected females, leading to embryonic lethality. "Rescue" of viability occurs if the female harbors the same Wolbachia strain. CI is caused by linked pairs of Wolbachia genes called CI factors (CifA and CifB). The co-evolution of CifA-CifB pairs may account in part for the incompatibility patterns documented in insects infected with different Wolbachia strains, but the molecular mechanisms remain elusive. Here, we use X-ray crystallography and AlphaFold to analyze the CI factors from Wolbachia strain wMel called CidAwMel and CidBwMel. Substituting CidAwMel interface residues with those from CidAwPip (from strain wPip) enables the mutant protein to bind CidBwPip and rescue CidBwPip-induced yeast growth defects, supporting the importance of CifA-CifB interaction in CI rescue. Sequence divergence in CidAwPip and CidBwPip proteins affects their pairwise interactions, which may help explain the complex incompatibility patterns of mosquitoes infected with different wPip strains.


Assuntos
Wolbachia , Animais , Citoplasma/genética , Citosol , Drosophila melanogaster/genética , Feminino , Masculino , Saccharomyces cerevisiae , Simbiose/genética , Wolbachia/genética , Wolbachia/metabolismo
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 44(1): 45-52, 2022 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-35300764

RESUMO

Objective To explore the clinical characteristics and treatment of Pseudomonas peritoneal dialysis-associated peritonitis(PsP). Methods The data of patients receiving peritoneal dialysis in four tertiary hospitals in Jilin province from 2015 to 2019 were retrospectively analyzed.According to the etiological classification,the patients with peritoneal dialysis-associated peritonitis(PDAP)were classified into PsP group and non-PsP group.The incidence of PsP was calculated,and the clinical characteristics and treatment outcomes of the two groups were compared.Kaplan-Meier method was used to draw the survival curve,and Cox regression was performed to analyze the risk factors affecting the technical failure of PsP.The treatment options of Pseudomonas aeruginosa-caused PDAP and the drug sensitivity of PsP were summarized. Results A total of 1530 peritoneal dialysis patients with complete data were included in this study,among which 439 patients had 664 times of PDAP.The incidence of PsP was 0.007 episodes/patient-year.PsP group had higher proportion of refractory peritonitis(41.38% vs.19.69%,P=0.005),lower cure rate(55.17% vs.80.79%, P=0.001),and higher extubation rate(24.14% vs.7.09%,P=0.003)than non-PsP group.The technical survival rate of PsP group was lower than that of non-PsP group(P<0.001).Multivariate Cox regression analysis showed that Pseudomonas aeruginosa was an independent risk factor for technical failure in patients with PsP(HR=9.020,95%CI=1.141-71.279,P=0.037).Pseudomonas was highly sensitive to amikacin,meropenem,and piperacillin-tazobactam while highly resistant to compound sulfamethoxazole,cefazolin,and ampicillin. Conclusion The treatment outcome of PsP is worse than that of non-PsP,and Pseudomonas aeruginosa is an independent risk factor for technical failure of PsP.


Assuntos
Diálise Peritoneal , Peritonite , Humanos , Diálise Peritoneal/efeitos adversos , Peritonite/tratamento farmacológico , Peritonite/etiologia , Pseudomonas , Estudos Retrospectivos , Resultado do Tratamento
16.
Pharm Biol ; 60(1): 274-281, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35138995

RESUMO

CONTEXT: Jinlida (JLD) as a traditional Chinese medicine formula has been used to treat type 2 diabetes mellitus (T2DM) and studies have shown its anti-obesity effect. OBJECTIVE: To investigate the therapeutic effects of JLD in a mouse model of non-alcoholic fatty liver (NAFL). MATERIALS AND METHODS: C57BL/6J mice were divided into three groups and fed a low-diet diet (LFD), high-fat diet (HFD), or HFD + JLD (3.8 g/kg) for 16 weeks, respectively. The free fatty acids-induced lipotoxicity in HepG2 cells were used to evaluate the anti-pyroptotic effects of JLD. The pharmacological effects of JLD on NAFL were investigated by pathological examination, intraperitoneal glucose and insulin tolerance tests, western blotting, and quantitative real-time PCR. RESULTS: In vivo studies showed that JLD ameliorated HFD-induced liver injury, significantly decreased body weight and enhanced insulin sensitivity and improved glucose tolerance. Furthermore, JLD suppressed both the mRNA expression of caspase-1 (1.58 vs. 2.90), IL-1ß (0.93 vs. 3.44) and IL-18 (1.34 vs. 1.60) and protein expression of NLRP3 (2.04 vs. 5.71), pro-caspase-1 (2.68 vs. 4.92) and IL-1ß (1.61 vs. 2.60). In vitro, JLD inhibited the formation of lipid droplets induced by 2 mM FFA (IC50 = 2.727 mM), reduced the protein expression of NLRP3 (0.74 vs. 2.27), caspase-1 (0.57 vs. 2.68), p20 (1.67 vs. 3.33), and IL-1ß (1.44 vs. 2.41), and lowered the ratio of p-IKB-α/IKB-α (0.47 vs. 2.19). CONCLUSION: JLD has a protective effect against NAFLD, which may be related to its anti-pyroptosis, suggesting that JLD has the potential as a novel agent in the treatment of NAFLD.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Piroptose/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica , Glucose/metabolismo , Células Hep G2 , Hepatócitos/patologia , Humanos , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos C57BL
17.
ACS Appl Mater Interfaces ; 14(7): 9864-9872, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35138795

RESUMO

Superhydrophobic TiO2 with great application potential is mainly obtained by surface modification with low surface energy organics, which is easily degraded under sunlight irradiation, which results in the loss of superhydrophobic properties. Herein, we developed a room-temperature pulsed chemical vapor deposition (pulsed CVD) method to develop amorphous TiO2-deposited TiO2 nanoparticles. The ultraviolet stability/ultraviolet-induced reversible wettability switch had been simultaneously realized by different and controllable deposition cycles of amorphous TiO2. The superhydrophobic properties of the organic-free TiO2 were determined by the micrometer-nanometer-sub-nanometer multiscale structure, the multiscale pore structure, and the large Young's contact angle resulting from carboxylic acid adsorption. Also, we found that the adsorption rate and adsorption stability of oxygen and water at the surface oxygen vacancies were the key to facilitate the reversible switching between superhydrophilic and superhydrophobic states, which was well demonstrated by experimental characterization and theoretical simulation. In addition, we also found that the resistance of dense amorphous TiO2 films on the TiO2 surface to the migration of photogenerated electrons and holes was the key to maintain the stable superhydrophobic properties of superhydrophobic TiO2 under ultraviolet illumination. The powders were strongly ground and the coating surface was rubbed on the surface of the sandpaper, which still maintained superhydrophobic properties, providing favorable conditions for the application of superhydrophobic TiO2. This work modulates the ultraviolet stability and dark/ultraviolet-induced switchable superhydrophobicity/superhydrophilicity of coated TiO2 by simply adjusting the number of deposition times in a pulsed CVD process for the first time, thus contributing to the development of organic-free superhydrophobic TiO2.

18.
Ultrason Sonochem ; 83: 105946, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35151194

RESUMO

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.


Assuntos
Glycyrrhiza , Chalconas , Isoflavonas , Fenóis , Extratos Vegetais/farmacologia , Solventes
19.
Med Sci Monit ; 28: e934975, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35058421

RESUMO

BACKGROUND This study aimed to investigate frontoparietal network (FPN) dysfunction in participants with migraine without aura (MwoA). MATERIAL AND METHODS We selected 48 age-, sex-, and education level-matched graduate students (24 participants with MwoA [MwoA group] and 24 healthy controls). RS-fMRI and independent component analysis were used to examine the FPN and to compare abnormal encephalic regional homogeneity values. The Mindful Attention Awareness Scale (MAAS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), and Self-Rating Scale of Sleep (SRSS) were used to evaluate attention, anxiety, depression, and sleep, respectively. Pearson's correlation was applied to evaluate the association between abnormal brain areas and the scores for each scale. RESULTS Neural function activity in encephalic regions of FPN showed abnormal changes in the MwoA group. The MwoA group had significantly lower MAAS scores (P<0.001), higher SAS scores (P<0.001), and higher SDS (P=0.06) and SRSS scores (P=0.26). In the MwoA group, functional activity of the right parietal lobule in the left FPN was positively correlated with MAAS scores (P=0.01) and negatively correlated with SAS (P=0.02). The orbital part of left inferior frontal gyrus activity in the right FPN was positively correlated with SDS (P=0.04) and SRSS (P<0.001). Right superior marginal gyrus activity in the right FPN was positively correlated with SDS (P=0.02). CONCLUSIONS Abnormal FPN function was correlated with attention, anxiety, depression, and sleep status in the MwoA group. These results offer further insights into the evaluation and treatment of MwoA.


Assuntos
Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Enxaqueca sem Aura/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Enxaqueca sem Aura/diagnóstico por imagem , Adulto Jovem
20.
Nat Prod Res ; 36(9): 2306-2313, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33089720

RESUMO

A new highly oxygenated germacranolide, carcerlane A (1), together with four known highly oxygenated germacranolides (2-5), was isolated from an ethanol extract of the whole plant of Carpesium nepalense var. lanatum (C.B.Clarke) Kitam. The structures were determined by HRESIMS and extensive analysis of their spectroscopic data including IR, 1 D and 2 D NMR spectra. To our best knowledge, it was the first time to report the phytochemical investigation on this plant. The anti-Alzheimer's disease (AD) activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. All the tested compounds showed that they have the anti-AD bioactivities of delaying worms paralysis.


Assuntos
Antineoplásicos Fitogênicos , Asteraceae , Antineoplásicos Fitogênicos/química , Asteraceae/química , Estrutura Molecular , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/farmacologia
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