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1.
J Agric Food Chem ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39295137

ABSTRACT

seco-pregnane C21 steroids exhibit high antiviral activity against the tobacco mosaic virus (TMV). However, the structural modification of seco-pregnane C21 steroids and the structure-activity relationship (SAR) of the modified compounds remain unevaluated. Hence, the present study investigated how variations in the original skeletons of natural seco-pregnane C21 steroids affect their antiviral activity. A series of glaucogenin C and A derivatives were designed and synthesized for the first time, and their anti-TMV activity was evaluated. Bioassay results showed that most of the newly designed derivatives exhibited good to excellent antiviral activity; among these derivatives, 5g, 5j, and 5l with higher antiviral activity than that of ningnanmycin emerged as new antiviral candidates. Reverse transcription-polymerase chain reaction and Western blotting assay revealed reduced levels of TMV coat protein (TMV-CP) gene transcription and TMV-CP protein expression, which confirmed the antiviral activity of these derivatives. These compounds also downregulated the expression of NtHsp70-1 and NtHsp70-061. Computational simulations indicated that 5l displayed strong van der Waals energy and electrostatic with the TMV coat protein, affording a lower binding energy (ΔGbind = -56.2 kcal/mol) compared with Ribavirin (ΔGbind = -47.6 kcal/mol). The SAR of these compounds was also evaluated, which demonstrated for the first time that substitutions at C-3 and double bonds of C-5/C-6 and C-13/C-18 are crucial for maintaining high anti-TMV activity.

2.
World J Gastrointest Surg ; 16(8): 2484-2493, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39220065

ABSTRACT

BACKGROUND: Gastric cancer remains a leading cause of cancer-related mortality globally. Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery. AIM: To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer, focusing on its potential to reduce trauma, accelerate recovery, and achieve comparable oncological outcomes. METHODS: This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023. The patients were divided into two groups: Minimally invasive surgery group (n = 102), who underwent laparoscopic gastrectomy, and open surgery group (n = 101), who underwent traditional open gastrectomy. We compared surgical indicators (surgical incision size, intraoperative blood loss, surgical duration, and number of lymph nodes dissected), recovery parameters (time to first flatus, time to start eating, time to ambulation, and length of hospital stay), immune function (levels of IgA, IgG, and IgM), intestinal barrier function (levels of D-lactic acid and diamine oxidase), and stress response (levels of C-reactive protein, interleukin-6, and procalcitonin). RESULTS: The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators, including smaller incisions, less blood loss, shorter surgery time, and more lymph nodes dissected (P < 0.05 for all). Recovery was also faster in the minimally invasive surgery group, with earlier return of bowel function, earlier initiation of diet, quicker mobilization, and shorter hospital stays (P < 0.05 for all). Furthermore, patients in the minimally invasive surgery group had better preserved immune function, superior intestinal barrier function, and a less pronounced stress response postoperatively (P < 0.05 for all). CONCLUSION: Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function, protecting intestinal barrier function, and mitigating the stress response compared to traditional open surgery. These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.

3.
Heliyon ; 10(14): e34219, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-39100436

ABSTRACT

This study presents a thermo-economic assessment of three low-global-warming-potential (GWP) substitutes, R1233zd(E), R1234ze(Z) and R1234ze(E), for R245fa used in organic Rankine cycle (ORC) systems, considering two models with different heat sources. The exhaust heat from a diesel generator is served as heat source of Model I, while the waste heat of exhaust and jacket cooling water are used as heat source of Model II. It is noted that the working pressure of R1234ze(E) is much higher than that of R1233zd(E), R1234ze(Z) and R245fa in a fixed evaporation-temperature range. Furthermore, the system using R1234ze(E) has the minimum net power output for Model I, while it turns into the maximum net power output for Model II. In addition, both R1234ze(Z) and R1233zd(E) can be used as good alternative working fluids for R245fa because R1234ze(Z), R1233zd(E) and R245fa have close working pressures, maximum net power outputs, and minimum levelized energy costs. Compared to Model I, LEC min of R1233ed(E) and R1234ze(Z) are reduced by 10.8 % and 9.9 % and PB min of R1233ed(E) and R1234ze(Z) are reduced by 11.5 % and 10.1 %, respectively, in Model II. However, R1233zd(E) has the highest minimum payback period for both Model I and Model II among the four working fluids investigated.

4.
Front Genet ; 15: 1436469, 2024.
Article in English | MEDLINE | ID: mdl-39092432

ABSTRACT

A dicentric chromosome is an abnormal chromosome with two centromeres on the same chromosome. It has been reported that dicentric chromosomes are specific biomarkers of radiation exposure, but dicentric chromosomes are rarely identified in newborns with multiple congenital anomalies. At 16 weeks of gestation, a 39-year-old pregnant woman (gravida 2, para 1) was referred to the prenatal diagnosis center for genetic counseling. The fetal ultrasonography indicated multiple anomalies. Subsequently, amniocentesis was performed, and the G-banding karyotype analysis showed a rare type of mosaicism. The C-banding karyotype analysis indicated a pseudo-dicentric chromosome X [psu dic (X; 18) (p11.2; p11.2)]. A single-nucleotide polymorphism array (SNP array) revealed three pathogenic copy number variations (CNVs). After genetic counseling, the parents chose to terminate this pregnancy. This study provides new evidence for a better understanding of the diagnosis of dicentric chromosomes and emphasizes on the importance of genetic counseling.

5.
Mitochondrial DNA B Resour ; 9(8): 995-999, 2024.
Article in English | MEDLINE | ID: mdl-39113746

ABSTRACT

The complete mitochondrial genome of Locastra muscosalis (Walker, 1866) was sequenced and characterized in this study, which was the first reported complete mitogenome of the genus Locastra. The mitogenome of L. muscosalis has a total length of 15,177 bp, encompassing 13 protein-coding genes (PCGs), 22 transfer RNA genes (tRNAs), 2 ribosomal RNA genes (rRNAs), and an A-T rich region. Phylogenetic analysis revealed that L. muscosalis is closely associated with Orthaga euadrusalis. These data will serve as a valuable foundation for future investigations into the Epipaschiinae and Pyralidae evolutionary history.

6.
Org Lett ; 26(35): 7408-7413, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39186015

ABSTRACT

A redox-neutral coupling of allyl alcohols with trifluoromethyl ketones has been developed via Ni-Ti bimetallic catalysis. This innovative method allows for the efficient synthesis of various ß-tertiary trifluoromethyl alcohol-substituted ketones with yields of up to 98%. The reaction is scalable and compatible with a wide range of substrates, including complex bioactive molecules. Mechanistic studies suggest that the rate-determining step involving ß-H elimination and the presence of the Ti-based Lewis acid, as well as a hydroxyl group on the substrates, is crucial for driving the reactivity of this transformation.

7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1186-1190, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39192417

ABSTRACT

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.


Subject(s)
Adaptor Proteins, Signal Transducing , Intracellular Signaling Peptides and Proteins , Mutation , Humans , Adaptor Proteins, Signal Transducing/genetics , Retrospective Studies , Intracellular Signaling Peptides and Proteins/genetics , Genetic Variation , Gene Frequency , Mutation, Missense , Myeloproliferative Disorders/genetics , Male , Hematologic Neoplasms/genetics
8.
BMC Pediatr ; 24(1): 537, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39174941

ABSTRACT

BACKGROUND: Due to regional and cultural differences, the current status of extremely preterm infants(EPIs) treatment across different areas of mainland China remains unclear. This study investigated the survival rate and incidence of major diseases among EPIs in the southwest area of Fujian province. METHOD: This retrospective and multicenter study collected perinatal data from EPIs with gestational ages between 22-27+ 6w and born in the southwest area of Fujian province. The study population was divided into 6 groups based on gestational age at delivery. The primary outcome was the survival status at ordered hospital discharge or correct gestational age of 40 weeks, and the secondary outcome was the incidence of major diseases. The study analyzed the actual survival status of EPIs in the area. RESULT: A total of 2004 preterm infants with gestational ages of 22-27+ 6 weeks were enrolled in this study. Among them, 1535 cases (76.6%) were born in the delivery room but did not survive, 469 cases (23.4%) were transferred to the neonatal department for treatment, 101 cases (5.0%) received partial treatment, and 368 cases (18.4%) received complete treatment. The overall all-cause mortality rate was 84.4% (1691/2004). The survival rate and survival rate without major serious disease for EPIs who received complete treatment were 85.1% (313/368) and 31.5% (116/318), respectively. The survival rates for gestational ages 22-22+ 6w, 23-23+ 6w, 24-24+ 6w, 25-25+ 6w, 26-26+ 6w, and 27-27+ 6w were 0%, 0%, 59.1% (13/22), 83% (39/47), 88.8% (87/98), and 89.7% (174/198), respectively. The survival rates without major serious disease were 0%, 0%, 9.1% (2/22), 19.1% (9/47), 27.6% (27/98), and 40.2% (78/194), respectively. CONCLUSION: The all-cause mortality of EPIs in the southwest area of Fujian Province remains high, with a significant number of infants were given up after birth in the delivery room being the main influencing factor. The survival rate of EPIs who received complete treatment at 25-27 weeks in the NICU was similar to that in developed countries. However, the survival rate without major serious disease was significantly lower compared to high-income countries.


Subject(s)
Gestational Age , Infant, Extremely Premature , Infant, Premature, Diseases , Humans , China/epidemiology , Retrospective Studies , Infant, Newborn , Female , Male , Infant, Premature, Diseases/epidemiology , Infant, Premature, Diseases/mortality , Infant, Premature, Diseases/therapy , Survival Rate , Incidence , Infant Mortality
9.
Inorg Chem ; 63(36): 16897-16907, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39197012

ABSTRACT

Exploiting a photocatalyst with high stability and excellent activity for Cr(VI) reduction under mild conditions is crucial yet challenging. Herein, the rigid aromatic multicarboxylate ligand with chromophore anthracene was selected to coordinate with multivalent metal ion manganese and to obtain a stable two-dimensional (2D) Mn-based metal-organic framework (MOF), LCUH-120, which can efficiently and quickly convert Cr(VI) into Cr(III) under light without the need for any additional photosensitizer. The efficient photosensitive anthracene group serves as a photosensitizer center and multivalent Mn(II) ion as a photocatalyst center in LCUH-120, and the conversion of Cr(VI) to Cr(III) can be realized completely in just 40 min. Specifically, the rate constant (k) and reduction rate of the Cr(VI) photocatalytic reaction can be high up to 0.134 min-1 and 2.50 mgCr(VI) g-1cata min-1 in an acidic environment (pH = 2), respectively. Compared to our previously reported three-dimensional (3D) Sm-MOF, LCUH-120 exhibits a significantly higher catalytic reaction rate, which might be ascribed to the fact that the photocatalyst center Mn node can improve the rate of electron transfer and promote the separation of holes and photogenerated electrons. In an acidic environment, the reaction mechanism can be verified through various contrast experiments and theoretical simulations.

10.
Zool Res ; 45(4): 937-950, 2024 07 18.
Article in English | MEDLINE | ID: mdl-39021082

ABSTRACT

Autophagy plays a pivotal role in diverse biological processes, including the maintenance and differentiation of neural stem cells (NSCs). Interestingly, while complete deletion of Fip200 severely impairs NSC maintenance and differentiation, inhibiting canonical autophagy via deletion of core genes, such as Atg5, Atg16l1, and Atg7, or blockade of canonical interactions between FIP200 and ATG13 (designated as FIP200-4A mutant or FIP200 KI) does not produce comparable detrimental effects. This highlights the likely critical involvement of the non-canonical functions of FIP200, the mechanisms of which have remained elusive. Here, utilizing genetic mouse models, we demonstrated that FIP200 mediates non-canonical autophagic degradation of p62/sequestome1, primarily via TAX1BP1 in NSCs. Conditional deletion of Tax1bp1 in fip200 hGFAP conditional knock-in (cKI) mice led to NSC deficiency, resembling the fip200 hGFAP conditional knockout (cKO) mouse phenotype. Notably, reintroducing wild-type TAX1BP1 not only restored the maintenance of NSCs derived from tax1bp1-knockout fip200 hGFAP cKI mice but also led to a marked reduction in p62 aggregate accumulation. Conversely, a TAX1BP1 mutant incapable of binding to FIP200 or NBR1/p62 failed to achieve this restoration. Furthermore, conditional deletion of Tax1bp1 in fip200 hGFAP cKO mice exacerbated NSC deficiency and p62 aggregate accumulation compared to fip200 hGFAP cKO mice. Collectively, these findings illustrate the essential role of the FIP200-TAX1BP1 axis in mediating the non-canonical autophagic degradation of p62 aggregates towards NSC maintenance and function, presenting novel therapeutic targets for neurodegenerative diseases.


Subject(s)
Autophagy-Related Proteins , Autophagy , Neural Stem Cells , Animals , Neural Stem Cells/physiology , Neural Stem Cells/metabolism , Mice , Autophagy/physiology , Autophagy-Related Proteins/genetics , Autophagy-Related Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Mice, Knockout , Sequestosome-1 Protein/metabolism , Sequestosome-1 Protein/genetics , Gene Expression Regulation , Neoplasm Proteins
12.
Ultrasound Med Biol ; 50(9): 1339-1345, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38824054

ABSTRACT

OBJECTIVE: This study aims to evaluate and compare the predictive accuracy of Sonazoid-contrast-enhanced ultrasound (CEUS) and Gd-EOB-DTPA-enhanced MRI for detecting microvascular invasion (MVI) in hepatocellular carcinoma (HCC). METHODS: In this single-center prospective study, we included 64 patients with histopathologically confirmed single HCC lesions. Based on post-operative pathologic data, patients were categorized into two groups: those with MVI (n = 21) and those without MVI (n = 43). The diagnostic efficacy of CEUS was compared with that of MRI in predicting MVI. RESULTS: Multifactorial analysis revealed that US features (tumor size > 4.35 cm, peritumoral enhancement, post-vascular ring enhancement, peak energy in the arterial phase of the difference between the margin area of HCC and distal liver parenchyma <-1.0 × 106 a.u), MRI features (rim enhancement, irregular tumor margin, and the halo sign) were all independent predictors of MVI (p < 0.05). The sensitivity and specificity of CEUS features in predicting MVI ranged from 61.9% to 86.4% and from 42.9% to 71.4%, respectively. For MRI features, the sensitivity and specificity ranged from 33.3% to 76.3% and from 54.7% to 90.5%, respectively. No statistically significant differences were observed in the area under the curve between CEUS and MRI (p > 0.05). Notably, peak energy of the difference showed the highest sensitivity at 86.4%, while the halo sign in MRI exhibited the highest specificity at 90.5%. CONCLUSION: Sonazoid-CEUS and Gd-EOB-DTPA-enhanced MRI demonstrate potential in predicting MVI in HCC lesions. Notably, CEUS showed higher sensitivity, whereas MRI displayed greater specificity in predicting MVI.


Subject(s)
Carcinoma, Hepatocellular , Contrast Media , Ferric Compounds , Gadolinium DTPA , Image Enhancement , Iron , Liver Neoplasms , Magnetic Resonance Imaging , Neoplasm Invasiveness , Oxides , Ultrasonography , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Male , Female , Magnetic Resonance Imaging/methods , Middle Aged , Prospective Studies , Ultrasonography/methods , Neoplasm Invasiveness/diagnostic imaging , Aged , Image Enhancement/methods , Sensitivity and Specificity , Predictive Value of Tests , Adult , Microvessels/diagnostic imaging , Liver/diagnostic imaging , Liver/pathology , Reproducibility of Results
13.
Patient Prefer Adherence ; 18: 1205-1215, 2024.
Article in English | MEDLINE | ID: mdl-38895638

ABSTRACT

Background: Kidney transplantation is a critical treatment for end-stage renal disease (ESRD), with health-promoting lifestyle (HPL) significantly impacting patient outcomes. HPL involves behaviors like regular exercise, balanced nutrition, stress management, and habit modification. However, few studies have analyzed the HPL of renal transplant recipients, addressing a significant gap in current research. Objective: This study aimed to determine the predictors of HPL in renal transplant recipients using the Chinese Health Promoting Lifestyle Profile (HPLP). Methods: This cross-sectional study enrolled renal transplant recipients completing the revised Chinese HPLP at organ transplant center in a tertiary hospital in Hunan Province of China between May 2022 and July 2022. Results: A total of 450 patients were included, comprising 256 males (56.9%), with a mean age of 44.85 ± 10.57 years. The mean score of self-actualization, health responsibility, interpersonal support, physical activity, stress management, nutrition, and overall HPLP were 15.27 ± 5.03 (possible range: 0-24), 11.41 ± 4.18 (possible range: 0-24), 11.61 ± 3.13 (possible range: 0-18), 7.53 ± 3.79 (possible range: 0-18), 12.68 ± 3.61 (possible range: 0-21), 11.17 ± 2.41 (possible range: 0-15), and 69.66 ± 16.98 (possible range: 0-120), respectively. Multivariate logistic regression analysis showed that urban residence (OR = 2.061, 95% CI: 1.350-3.148, P = 0.001), non-smoking after transplantation (OR = 2.010, 95% CI: 1.123-3.600, P = 0.019) and two post-transplant complications (OR=0.387, 95% CI: 0.218-0.689, P = 0.001). Conclusion: Although renal transplant recipients exhibit a moderate level of HPL, targeted interventions are essential to improve these behaviors. These interventions should focus especially on individuals from rural households, post-transplant smokers, and those experiencing post-transplant complications, to enhance their quality of life and clinical outcomes.

14.
Proc Natl Acad Sci U S A ; 121(24): e2321619121, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38833475

ABSTRACT

Angiotensin-convertingenzyme 2 (ACE2) has dual functions, regulating cardiovascular physiology and serving as the receptor for coronaviruses. Bats, the only true flying mammals and natural viral reservoirs, have evolved positive alterations in traits related to both functions of ACE2. This suggests significant evolutionary changes in ACE2 during bat evolution. To test this hypothesis, we examine the selection pressure in ACE2 along the ancestral branch of all bats (AncBat-ACE2), where powered flight and bat-coronavirus coevolution occurred, and detect a positive selection signature. To assess the functional effects of positive selection, we resurrect AncBat-ACE2 and its mutant (AncBat-ACE2-mut) created by replacing the positively selected sites. Compared to AncBat-ACE2-mut, AncBat-ACE2 exhibits stronger enzymatic activity, enhances mice's performance in exercise fatigue, and shows lower affinity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Our findings indicate the functional pleiotropy of positive selection in the ancient ACE2 of bats, providing an alternative hypothesis for the evolutionary origin of bats' defense against coronaviruses.


Subject(s)
Angiotensin-Converting Enzyme 2 , Chiroptera , Selection, Genetic , Chiroptera/virology , Chiroptera/genetics , Animals , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Mice , Genetic Pleiotropy , Evolution, Molecular , SARS-CoV-2/genetics , COVID-19/virology , COVID-19/genetics , Coronavirus/genetics , Humans , Phylogeny
15.
J Leukoc Biol ; 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38833591

ABSTRACT

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

16.
Front Neurosci ; 18: 1324047, 2024.
Article in English | MEDLINE | ID: mdl-38919910

ABSTRACT

Currently, there is no established system for quantifying patterns of ocular ductions. This poses challenges in tracking the onset and evolution of ocular motility disorders, as current clinical methodologies rely on subjective observations of individual movements. We propose a protocol that integrates image processing, a statistical framework of summary indices, and criteria for evaluating both cross-sectional and longitudinal differences in ductions to address this methodological gap. We demonstrate that our protocol reliably transforms objective estimates of ocular rotations into normative patterns of total movement area and movement symmetry. This is a critical step towards clinical application in which our protocol could first diagnose and then track the progression and resolution of ocular motility disorders over time.

17.
18.
Int J Hematol ; 120(2): 157-166, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38814500

ABSTRACT

G protein pathway suppressor 2 (GPS2) has been shown to play a pivotal role in human and mouse definitive erythropoiesis in an EKLF-dependent manner. However, whether GPS2 affects human primitive erythropoiesis is still unknown. This study demonstrated that GPS2 positively regulates erythroid differentiation in K562 cells, which have a primitive erythroid phenotype. Overexpression of GPS2 promoted hemin-induced hemoglobin synthesis in K562 cells as assessed by the increased percentage of benzidine-positive cells and the deeper red coloration of the cell pellets. In contrast, knockdown of GPS2 inhibited hemin-induced erythroid differentiation of K562 cells. GPS2 overexpression also enhanced erythroid differentiation of K562 cells induced by cytosine arabinoside (Ara-C). GPS2 induced hemoglobin synthesis by increasing the expression of globin and ALAS2 genes, either under steady state or upon hemin treatment. Promotion of erythroid differentiation of K562 cells by GPS2 mainly relies on NCOR1, as knockdown of NCOR1 or lack of the NCOR1-binding domain of GPS2 potently diminished the promotive effect. Thus, our study revealed a previously unknown role of GPS2 in regulating human primitive erythropoiesis in K562 cells.


Subject(s)
Cell Differentiation , Erythropoiesis , Hemin , Leukemia, Erythroblastic, Acute , Nuclear Receptor Co-Repressor 1 , Humans , 5-Aminolevulinate Synthetase/genetics , 5-Aminolevulinate Synthetase/metabolism , Erythroid Cells/metabolism , Erythroid Cells/cytology , Erythropoiesis/genetics , Gene Knockdown Techniques , Hemin/pharmacology , Hemoglobins/metabolism , Intracellular Signaling Peptides and Proteins , K562 Cells , Leukemia, Erythroblastic, Acute/pathology , Leukemia, Erythroblastic, Acute/metabolism , Leukemia, Erythroblastic, Acute/genetics , Nuclear Receptor Co-Repressor 1/metabolism , Nuclear Receptor Co-Repressor 1/genetics
19.
J Pharm Sci ; 113(8): 2513-2523, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38768757

ABSTRACT

Nanoparticles composed of Levan and Dolutegravir (DTG) have been successfully synthesized using a spray drying procedure specifically designed for milk/food admixture applications. Levan, obtained from the microorganism Bacillus subtilis, was thoroughly characterized using MALDI-TOF and solid-state NMR technique to confirm its properties. In the present study, this isolated Levan was utilized as a carrier for drug delivery applications. The optimized spray-dried nanoparticles exhibited a smooth surface morphology with particle sizes ranging from 195 to 329 nm. In the in-vitro drug release experiments conducted in water media, the spray-dried nanoparticles showed 100 % release, whereas the unprocessed drug exhibited only 50 % release at the end of 24 h. Notably, the drug release in milk was comparable to that in plain media, indicating the compatibility. The improved dissolution rate observed for the nanoparticles could be attributed to the solid-state conversion (confirmed by XRD analysis) of DTG from its crystalline to amorphous state. The stability of the drug was verified using Fourier Transform Infra-Red Spectroscopy and Thermogravimetry-Differential Scanning Calorimetry analysis. To evaluate the in-vitro cellular toxicity, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was conducted, which revealed the CC50 value of 88.88 ± 5.10 µg/mL for unprocessed DTG and 101.08 ± 37.37 µg/mL for DTG nanoparticles. These results indicated that the toxicity of the nanoparticles was comparable to the unprocessed drug. Furthermore, the anti-HIV activity of the nanoparticles in human cell lines was found to be similar to that of the pure drug, emphasizing the therapeutic efficacy of DTG in combating HIV.


Subject(s)
Anti-HIV Agents , Fructans , Heterocyclic Compounds, 3-Ring , Milk , Nanoparticles , Oxazines , Piperazines , Pyridones , Pyridones/chemistry , Oxazines/chemistry , Piperazines/chemistry , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/administration & dosage , Humans , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Animals , Nanoparticles/chemistry , Fructans/chemistry , Milk/chemistry , Drug Liberation , Drug Carriers/chemistry , Particle Size , Bacillus subtilis/drug effects , Spray Drying , Drug Delivery Systems/methods
20.
J Proteomics ; 301: 105191, 2024 06 15.
Article in English | MEDLINE | ID: mdl-38697285

ABSTRACT

Cystic echinococcosis is a zoonotic disease resulting from infection caused by the larval stage of Echinococcus granulosus. This study aimed to assess the specific proteins that are potential candidates for the development of a vaccine against E. granulosus. The data-independent acquisition approach was employed to identify differentially expressed proteins (DEPs) in E. granulosus samples. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was employed to identify several noteworthy proteins. Results: The DEPs in E. granulosus samples were identified (245 pericystic wall vs. parasite-free yellowish granuloma (PYG, 1725 PY vs. PYG, 2274 PN vs. PYG). Further examination of these distinct proteins revealed their predominant enrichment in metabolic pathways, amyotrophic lateral sclerosis, and neurodegeneration-associated pathways. Notably, among these DEPs, SH3BGRL, MST1, TAGLN2, FABP5, UBE2V2, and RARRES2 exhibited significantly higher expression levels in the PYG group compared with the PY group (P < 0.05). The findings may contribute to the understanding of the pathological mechanisms underlying echinococcosis, providing valuable insights into the development of more effective diagnostic tools, treatment modalities, and preventive strategies. SIGNIFICANCE: CE is a major public health hazard in the western regions of China, Central Asia, South America, the Mediterranean countries, and eastern Africa. Echinococcus granulosus is responsible for zoonotic disease through infection Our analysis focuses on the proteins in various samples by data-dependent acquisition (DIA) for proteomic analysis. The importance of this research is to develop new strategies and targets to protect against E. granulosus infections in humans.


Subject(s)
Echinococcus granulosus , Proteomics , Proteomics/methods , Humans , Echinococcus granulosus/metabolism , Animals , Helminth Proteins/metabolism , Helminth Proteins/analysis , Echinococcosis, Hepatic/metabolism , Echinococcosis, Hepatic/parasitology , Proteome/analysis , Proteome/metabolism
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