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1.
Clinics (Sao Paulo) ; 79: 100486, 2024.
Article in English | MEDLINE | ID: mdl-39277981

ABSTRACT

OBJECTIVE: This study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). METHODS: This prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. RESULTS: Serum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. CONCLUSION: Serum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.


Subject(s)
Adenocarcinoma, Follicular , Basic Helix-Loop-Helix Transcription Factors , Biomarkers, Tumor , Chitinase-3-Like Protein 1 , Hypoxia-Inducible Factor 1, alpha Subunit , Neoplasm Invasiveness , Predictive Value of Tests , Humans , Chitinase-3-Like Protein 1/blood , Female , Male , Hypoxia-Inducible Factor 1, alpha Subunit/blood , Middle Aged , Prognosis , Adult , Adenocarcinoma, Follicular/blood , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/mortality , Prospective Studies , Basic Helix-Loop-Helix Transcription Factors/blood , Biomarkers, Tumor/blood , Thyroid Neoplasms/blood , Thyroid Neoplasms/pathology , Thyroid Neoplasms/mortality , Aged , Neoplasm Recurrence, Local/blood , Neoplasm Recurrence, Local/pathology , Enzyme-Linked Immunosorbent Assay , Reference Values , Young Adult , Statistics, Nonparametric , ROC Curve
2.
Cytokine ; 182: 156726, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39111113

ABSTRACT

PURPOSE: NK cells are essential for the detection, identification and prediction of cancer. However, so far, there is no prognostic risk model based on NK cell-related genes to predict the prognosis and treatment outcome of DLBCL patients. This study aimed to explore a risk assessment model that could accurately predict the prognosis and treatment efficacy of DLBCL. METHODS: Bioinformatics analysis of the expression profiles of DLBCL samples in the GEO database was performed. Cox regression and LASSO regression analysis were used to determine NK cell-related genes associated with patient's prognosis. Based on these genes, a risk assessment model was constructed to predict the prognosis of patients and the effectiveness of treatment. Finally, qRT-PCR was used to verify the expression of gene tags in clinical samples. RESULTS: We identified seven prognosis-related NK cell-related genes (MAP2K1, PRKCB, TNFRSF10B, IL18, LAMP1, RASGRP1, and SP110), and DLBCL patients were divided into low- and high-risk groups based on these genes. Survival analysis showed that the prognosis of patients with low-risk group was better. Pathway enrichment analysis showed that the differentially expressed genes between the two risk groups were related to immune response pathways. Compared with the high-risk group, the low-risk group had higher infiltration of immune cells in tumor tissues. Besides, compared with high-risk group, low-risk patients by immunotherapy or other commonly used anti-tumor drugs might have better efficacy after treatment. In addition, qRT-PCR showed that the expression of risk genes including TNFRSF10B, IL18 and LAMP1 were significantly increased in most DLBCL samples compared to control samples, while the expression of protective genes including MAP2K1, PRKCB, RASGRP1 and SP110 were significantly decreased. CONCLUSION: The NK cell-related gene signatures were proved to be a reliable indicator of the success of immunotherapy in patients with DLBCL, thus providing a unique evaluation method.


Subject(s)
Killer Cells, Natural , Lymphoma, Large B-Cell, Diffuse , Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/immunology , Killer Cells, Natural/immunology , Prognosis , Treatment Outcome , Gene Expression Regulation, Neoplastic , Male , Female , Transcriptome/genetics , Computational Biology/methods , Gene Expression Profiling , Survival Analysis , Biomarkers, Tumor/genetics , DNA-Binding Proteins , Guanine Nucleotide Exchange Factors
3.
Parasite ; 31: 50, 2024.
Article in English | MEDLINE | ID: mdl-39212527

ABSTRACT

Captive and free-living wildlife serve as significant hosts for Giardia duodenalis. Asiatic black bears, valued for their economic and medicinal importance, are extensively farmed in China and also prevalent in zoos. However, studies on G. duodenalis in these animals in China are limited. Here, 218 feces samples of Asiatic black bears were collected: 36 from a zoo in Heilongjiang Province, and 182 from a farm in Fujian Province. Nested PCR of the SSU rRNA gene, followed by sequencing, was employed to determine the frequency and assemblage distribution of G. duodenalis. Positive samples underwent further analysis through multilocus genotyping (MLG) by amplifying the genes for glutamate dehydrogenase (gdh), ß-giardin (bg), and triosephosphate isomerase (tpi). Of the 218 samples, G. duodenalis was detected in 22 cases at the SSU rRNA gene locus, including three from Heilongjiang and 19 from Fujian. Three assemblages were identified: A (n = 1), B (n = 16), and E (n = 2) in Fujian; and B (n = 3) in Heilongjiang. Out of the 22 positive samples, 20, 19, and 9 were effectively amplified and sequenced across the tpi, gdh, and bg loci, respectively. Seven samples were genotyped successfully at all three loci, identifying MLG-B1 (n = 1), MLG-B2 (n = 1), and MLG-B3 (n = 1), MLG-B4 (n = 1), MLG-B5 (n = 2), and MLG-B6 (n = 1) as the six assemblage B MLGs. This study marks the first documentation of G. duodenalis in Asiatic black bears in captivity in Fujian and Heilongjiang. The identification of zoonotic assemblages A and B, along with E, underscores potential public health concerns.


Title: Prévalence et assemblages de Giardia duodenalis chez les ours noirs d'Asie (Ursus thibetanus) d'élevage et de zoos dans les provinces chinoises du Heilongjiang et du Fujian. Abstract: Les faunes captive et libre incluent des hôtes importants pour Giardia duodenalis. Les ours noirs d'Asie, appréciés pour leur importance économique et médicinale, sont couramment élevés en Chine et répandus dans les zoos. Cependant, les études sur G. duodenalis chez ces animaux en Chine sont limitées. Ici, 218 échantillons d'excréments d'ours noirs d'Asie ont été collectés, 36 dans un zoo de la province du Heilongjiang et 182 dans une ferme de la province du Fujian. La PCR imbriquée de l'ARNr SSU, suivie d'un séquençage, a été utilisée pour déterminer la fréquence et la distribution des assemblages de G. duodenalis. Les échantillons positifs ont subi une analyse plus approfondie par génotypage multilocus (MLG) en amplifiant les gènes de la glutamate déshydrogénase (gdh), de la ß-giardine (bg) et de la triosephosphate isomérase (tpi). Sur les 218 échantillons, G. duodenalis a été détecté dans 22 cas par le locus du gène de l'ARNr SSU, dont trois du Heilongjiang et 19 du Fujian. Trois assemblages ont été identifiés : A (n = 1), B (n = 16) et E (n = 2) dans le Fujian, et B (n = 3) dans le Heilongjiang. Sur les 22 échantillons positifs, 20, 19 et 9 ont été efficacement amplifiés et séquencés respectivement pour les loci tpi, gdh et bg. Sept échantillons ont été génotypés avec succès sur les trois loci, identifiant MLG-B1 (n = 1), MLG-B2 (n = 1) et MLG-B3 (n = 1), MLG-B4 (n = 1), MLG- B5 (n = 2) et MLG-B6 (n = 1) comme les six assemblages MLG B. Cette étude marque la première investigation de G. duodenalis chez les ours noirs d'Asie en captivité au Fujian et au Heilongjiang. L'identification des assemblages zoonotiques A et B, ainsi que E, souligne des problèmes potentiels de santé publique.


Subject(s)
Animals, Zoo , Feces , Giardia lamblia , Giardiasis , Ursidae , Animals , China/epidemiology , Giardia lamblia/genetics , Giardia lamblia/isolation & purification , Giardia lamblia/classification , Giardiasis/veterinary , Giardiasis/parasitology , Giardiasis/epidemiology , Animals, Zoo/parasitology , Prevalence , Ursidae/parasitology , Feces/parasitology , Genotype , Phylogeny , Triose-Phosphate Isomerase/genetics , Farms , Glutamate Dehydrogenase/genetics , DNA, Protozoan , Protozoan Proteins/genetics , Polymerase Chain Reaction/veterinary , Multilocus Sequence Typing , Cytoskeletal Proteins/genetics
4.
Cancer Gene Ther ; 2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39183354

ABSTRACT

Metastatic rhabdomyosarcoma is associated with poor survival and unsatisfactory treatment outcomes. Therefore, new immunotherapeutic methods are urgently required. Fibroblast growth factor receptor 4 (FGFR4), a new therapeutic target for rhabdomyosarcoma, plays a crucial role in its onset and development. This study aimed to generate FGFR4 single-chain variable fragment-based chimeric antigen receptor (CAR) T cells without causing evident toxicity and incorporating an inducible caspase-9 (iCasp9) suicide gene system to enhance their safety. FGFR4 antigen expression was evaluated in normal murine tissues, normal human tissues, and specimens from patients with rhabdomyosarcoma. Combined with a 4-1BB co-stimulatory domain, a CD3ζ signaling domain, and an iCasp9 suicide gene, CAR-T cells with an FGFR4-specific single-chain variable fragment were developed. The specific cytotoxic effects, T-cell proliferation, cytokine secretion, apoptosis induction by chemical dimerization (AP20187), and toxicity of FGFR4 CAR-T cells were investigated in vitro and in vivo. FGFR4 CAR-T cells generated a variety of immune-promoting cytokines, including tumor necrosis factor α, interleukin 2, and interferon γ, and displayed effective cytotoxic activity against FGFR4-overexpressing rhabdomyosarcoma cells in vitro. FGFR4 CAR-T cells were relatively effective against FGFR4-overexpressing rhabdomyosarcoma, with tumor regression and poor survival in a subcutaneous xenograft model. The iCasp9 gene was incorporated into FGFR4 CAR-T cells and it was demonstrated that effective and reliable suicide gene activity depends on the administration of AP20187. By making use of the cross-reaction of FGFR4 CAR-T cells with murine FGFR4 in a syngeneic tumor model, this study found that FGFR4 CAR-T cells could regulate the growth of tumors without evident toxicity. Our study demonstrates that FGFR4 is a prospective target for CAR-T cell therapy in rhabdomyosarcoma without serious on-target off-tumor toxicity. FGFR4 CAR-T cells with the iCasp9 suicide gene system as a safety switch to limit toxicity may broaden the clinical applications of cellular therapy.

5.
Front Vet Sci ; 11: 1427490, 2024.
Article in English | MEDLINE | ID: mdl-39015103

ABSTRACT

Introduction: Globally, rodents and shrew populations constitute crucial elements of diverse environments and animal communities. It is imperative to study their population dynamics to mitigate any potential negative impact on humans, as they can be involved in the transmission of critical zoonotic agents, such as Blastocystis. Therefore, this study aimed to identify the prevalence and genetic composition of Blastocystis in wild rodents and shrews residing in the Zhejiang provinces of China. Methods: A total of 652 wild rodents and and shrews were captured from three different regions in Zhejiang Province from April 1st to October 31, 2023. The DNA was isolated by collecting fresh feces from the intestines of each rodent or and shrew. Rodent and shrew species were examined by vertebrate cytochrome b (cytb) analysis and PCR amplification. Blastocystis was also found in all fecal samples using PCR analysis and sequencing of the partial small subunit of ribosomal RNA (SSU rRNA) gene. Results: Among all the samples, 6.6% (43/652) showed a positive result for Blastocystis. In the results, 6 species of rodent and shrew were identified with Blastocystis, including Apodemus agrarius (n = 36) (2.8%), Niviventer confucianus (n = 75) (17.3%), Rattus losea (n = 18) (5.6%), R. norvegicus (n = 155) (2.6%), R. tanezumi (n = 86) (3.5%), and Suncus murinus (n = 282) (7.4%). The existence of 6 Blastocystis subtypes, ST4 (n = 33), ST1 (4), ST7 (n = 3), ST2 (n = 1), ST3 (n = 1), and ST5 (n = 1), were confirmed by sequence analysis. Discussion: Based on the molecular data obtained, the wild rodents and shrews under investigation were found to be concurrently infected with zoonotic subtypes of Blastocystis, including ST1 to ST5 and ST7. This suggests that these animals could potentially pose a zoonotic threat to humans and other animals susceptible to Blastocystis infection.

6.
J Phys Chem Lett ; 15(25): 6467-6475, 2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38869188

ABSTRACT

Photoexcitation induces intricate changes in both the real and imaginary components of the complex refractive index of thin film materials, which is essential for interpreting transient spectral features. Here, we employ a Kramers-Kronig-based analytical approach to elucidate light-induced changes in the complex refractive index from transient transmission spectra of thin films. Using gold-perovskite films as model systems, we conduct experimental measurements of transient transmission spectra for both individual gold and perovskite films, as well as for the bilayer heterostructure. Our analysis reveals significant changes in the refractive index and absorption for these systems. Notably, we observe negligible photocarrier transfer between the gold and perovskite layers based on transient spectroscopic analysis. These findings have implications for the design and optimization of bilayer heterostructures in optoelectronic applications. This work highlights the importance of spectroscopic techniques in studying the photophysical properties of heterostructure films.

7.
Mol Pharm ; 21(8): 3866-3879, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-38920116

ABSTRACT

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evaded the efficacy of previously developed antibodies and vaccines, thus remaining a significant global public health threat. Therefore, it is imperative to develop additional antibodies that are capable of neutralizing emerging variants. Nanobodies, as the smallest functional single-domain antibodies, exhibit enhanced stability and penetration ability, enabling them to recognize numerous concealed epitopes that are inaccessible to conventional antibodies. Herein, we constructed an immune library based on the immunization of alpaca with the S1 subunit of the SARS-CoV-2 spike protein, from which two nanobodies, Nb1 and Nb2, were selected using phage display technology for further characterization. Both nanobodies, with the binding residues residing within the receptor-binding domain (RBD) region of the spike, exhibited high affinity toward the S1 subunit. Moreover, they displayed cross-neutralizing activity against both wild-type SARS-CoV-2 and 10 ο variants, including BA.1, BA.2, BA.3, BA.5, BA.2.75, BF.7, BQ.1, EG.5.1, XBB.1.5, and JN.1. Molecular modeling and dynamics simulations predicted that both nanobodies interacted with the viral RBD through their complementarity determining region 1 (CDR1) and CDR2. These two nanobodies are novel tools for the development of therapeutic and diagnostic countermeasures targeting SARS-CoV-2 variants and potentially emerging coronaviruses.


Subject(s)
Antibodies, Neutralizing , COVID-19 , SARS-CoV-2 , Single-Domain Antibodies , Spike Glycoprotein, Coronavirus , Single-Domain Antibodies/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/chemistry , Animals , COVID-19/immunology , COVID-19/therapy , COVID-19/virology , COVID-19/diagnosis , Humans , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Camelids, New World/immunology , Epitopes/immunology
8.
J Gen Physiol ; 156(7)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38814250

ABSTRACT

The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease (COPD) but was recently found to possess broad-spectrum off-target effects. Here, we show that, under physiological Ca2+ (200-500 nM) and voltages, niclosamide acutely potentiates TMEM16A. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering clinical applications of niclosamide as a TMEM16A inhibitor. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation and provides insights into developing specific TMEM16A modulators to treat human diseases.


Subject(s)
Anoctamin-1 , Niclosamide , Vasoconstriction , Niclosamide/pharmacology , Anoctamin-1/metabolism , Anoctamin-1/genetics , Animals , Mice , Humans , Vasoconstriction/drug effects , HEK293 Cells , Binding Sites , Calcium/metabolism , Mesenteric Arteries/drug effects , Mesenteric Arteries/metabolism , Muscle, Smooth, Vascular/drug effects , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolism , Male
9.
Virol Sin ; 39(3): 414-421, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38677713

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. This study utilized various techniques such as luciferase immunoprecipitation system (LIPS), immunofluorescence â€‹assay (IFA), and western â€‹blot (WB) to detect accessory protein-specific antibodies in sera of COVID-19 patients. Specific antibodies to proteins 3a, 3b, 7b, 8 and 9c can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. Antibodies against proteins 3a and 7b were only detected in ICU patients, which may serve as a marker for predicting disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for protein detection assays and their role in pathogenesis.


Subject(s)
Antibodies, Viral , COVID-19 , Disease Models, Animal , Immunity, Humoral , SARS-CoV-2 , Animals , Humans , SARS-CoV-2/immunology , COVID-19/immunology , COVID-19/virology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Mice , Female , Mice, Inbred BALB C , Male , Middle Aged , Antibodies, Neutralizing/immunology , Antibodies, Neutralizing/blood , Adult , Aged
10.
Microorganisms ; 12(4)2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38674755

ABSTRACT

Globally, Enterocytozoon bieneusi has been detected in humans and various animal hosts. Wild rats and shrews have the potential to act as carriers of E. bieneusi, facilitating the parasite's transmission to humans and domestic animals. We aimed to investigate the prevalence of E. bieneusi in 652 wild rats and shrews from Zhejiang Province, China, by amplifying the internal transcribed spacer (ITS) region of rDNA through polymerase chain reaction (PCR). To determine animal species, we amplified the Cytochrome b (Cyt-b) gene in their fecal DNA using PCR. Furthermore, we determined the genotype of E. bieneusi by amplifying the ITS region of rDNA through PCR. Genetic traits and zoonotic potential were evaluated using similarity and phylogenetic analyses. Suncus murinus (n = 282) and five rat species, Rattus losea (n = 18), Apodemus agrarius (n = 36), Rattus tanezumi (n = 86), Rattus norvegicus (n = 155), and Niviventer niviventer (n = 75), were identified. The average infection rate of E. bieneusi was 14.1% (92/652) with 18.1% (51/282) in S. murinus and 11.1% (41/370) in rats (27.8% in R. losea, 22.2% in A. agrarius, 10.5% in R. tanezumi, 8.4% in R. norvegicus, and 8.0% in N. niviventer). Thirty-three genotypes were identified, including 16 known genotypes. The most commonly known genotypes were HNR-VI (n = 47) and Peru11 (n = 6). Type IV, KIN-1, SHW7, and HNPL-II were each found in two samples, while Macaque4, CH5, K, Henan-III, Henan-V, HNP-II, HNPL-I, HNPL-III, HNHZ-II, and HNHZ-III were each found in one sample. Additionally, 17 novel genotypes were discovered: WZR-VIII (n = 5), WZR-I to WZR-VII, WZR-IX to WZR-XII, and WZSH-I to WZSH-V (n = 1 each). Those 33 genotypes were divided into three groups: Group 1 (n = 25), Group 2 (n = 3), and Group 13 (n = 5). The initial report underscores the extensive occurrence and notable genetic diversity of E. bieneusi in wild rats and shrews from Zhejiang province, China. These results suggest that these animals play a pivotal role in the transmission of E. bieneusi. Furthermore, animals carrying the zoonotic genotypes of E. bieneusi pose a serious threat to residents.

11.
Article in English | MEDLINE | ID: mdl-38598173

ABSTRACT

Motivated by the surging demand for low-temperature waste heat harvesting, materials with both prominent thermoelectric and good mechanical properties are preferred in practical applications. In this present work, the composite exploration of Te-doped Mg3.2Bi1.5Sb0.5-x vol % nanosized SiC (x = 0, 0.05, 0.1, 0.2, and 0.5) was carried out, where nanosized SiC is physically dispersed in the matrix in the form of a second phase. SiC second phase compositing further optimized the matrix carrier concentration, resulting in a higher power factor in the service temperature range (the highest value from 28.9 to 31.7 µW cm-1 K-2), and the (ZT)ave from 0.91 to 0.96 compared with the matrix sample. In addition, the SiC second phase effectively enhanced the mechanical properties of composite materials, including flexural strength, microhardness, and modulus. Because of the simultaneous optimization of thermoelectric and mechanical properties, the overall performance of Te-doped Mg3.2Bi1.5Sb0.5-0.05 vol % SiC composite is leveraged to meet special requirements of power generation. It is expected that the addition of SiC should be broadly applicable to address the physical performance in other thermoelectric systems.

12.
Tumori ; 110(4): 227-240, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38183180

ABSTRACT

The microenvironment of diffuse large B-cell lymphoma (DLBCL) is composed of various components, including immune cells and immune checkpoints, some of which have been correlated with the prognosis of DLBCL, but their results remain controversial. Therefore, we conducted a systematic review and meta-analysis to investigate the association between the microenvironment and prognosis in DLBCL. We searched PubMed, Web of Science, and EMBASE for relevant articles between 2001 and 2022. Twenty-five studies involving 4495 patients with DLBCL were included in the analysis. This meta-analysis confirmed that high densities of Foxp3+Tregs and PD-1+T cells are good indicators for overall survival (OS) in DLBCL, while high densities of programmed cell death protein ligand1(PD-L1)-positive expression cells and T-cell immunoglobulin-and mucin domain-3-containing molecule 3 (TIM-3)-positive expression tumor-infiltrating cells (TILs) play a contrary role in OS. Additionally, higher numbers of T-cell intracytoplasmic antigen-1(TIA-1)-positive expression T cells imply better OS and progression-free survival (PFS), while high numbers of lymphocyte activation gene(LAG)-positive expression TILs predict bad OS and PFS. Various non-tumoral cells in the microenvironment play important roles in the prognosis of DLBCL.


Subject(s)
Biomarkers, Tumor , Lymphoma, Large B-Cell, Diffuse , Tumor Microenvironment , Humans , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/metabolism , Lymphoma, Large B-Cell, Diffuse/mortality , Prognosis , Tumor Microenvironment/immunology , Biomarkers, Tumor/metabolism , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism
13.
Adv Sci (Weinh) ; 11(9): e2303366, 2024 03.
Article in English | MEDLINE | ID: mdl-38105421

ABSTRACT

To combat SARS-CoV-2 variants and MERS-CoV, as well as the potential re-emergence of SARS-CoV and spillovers of sarbecoviruses, which pose a significant threat to global public health, vaccines that can confer broad-spectrum protection against betacoronaviruses (ß-CoVs) are urgently needed. A mosaic ferritin nanoparticle vaccine is developed that co-displays the spike receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 Wild-type (WT) strain and evaluated its immunogenicity and protective efficacy in mice and nonhuman primates. A low dose of 10 µg administered at a 21-day interval induced a Th1-biased immune response in mice and elicited robust cross-reactive neutralizing antibody responses against a variety of ß-CoVs, including a series of SARS-CoV-2 variants. It is also able to effectively protect against challenges of SARS-CoV, MERS-CoV, and SARS-CoV-2 variants in not only young mice but also the more vulnerable mice through induction of long-lived immunity. Together, these results suggest that this mosaic 3-RBD nanoparticle has the potential to be developed as a pan-ß-CoV vaccine.


Subject(s)
Coronavirus Infections , Middle East Respiratory Syndrome Coronavirus , Nanoparticles , Viral Vaccines , Humans , Animals , Mice , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/prevention & control , SARS-CoV-2 , Middle East Respiratory Syndrome Coronavirus/chemistry , Models, Animal
14.
Sci Total Environ ; 904: 166744, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37659528

ABSTRACT

BACKGROUND: Little is known about the associations of exposure to fine particulate matter (PM2.5) and its constituents with ovarian reserve, and the potential susceptible window of exposure remains unclear. METHODS: We performed a retrospective cohort study of 5189 women who attended a fertility center in Hubei, China, during 2019-2022, and estimated concentrations of PM2.5 and its major constituents during the development of follicles (4th-6th month [W1], 0-4th month [W2], 0-6th month [W3]) and 1-year before measurement (W4) based on Tracking Air Pollution in China database. We used multivariable linear regression and logistic regression models to examine the associations of PM2.5 and its constituent exposures with anti-Müllerian hormone (AMH), the preferred indicator of ovarian reserve. RESULTS: We observed significantly decreased AMH levels associated with increasing PM2.5 concentrations, with the percent changes (95 % confidence intervals [CIs]) of 1.99 % (0.24 %-3.71 %) during W1 and 3.99 % (0.74 %-7.15 %) during W4 for per 10 µg/m3 increases in PM2.5.When PM2.5 exposure levels were equal to 50th percentile (32.6-42.3 µg/m3) or more, monotonically decreased AMH levels and increased risks of low AMH were seen with increasing PM2.5 concentrations during W1 and W4 (P < 0.05). Black carbon (BC), ammonium (NH4+), nitrate (NO3-), and organic matter (OM) during W1, and NH4+, NO3-, as well as sulfate (SO42-) during W4 were significantly associated with decreased AMH. Moreover, PM2.5 and SO42- exposures during W4 were positively associated with low AMH. Additionally, the associations were stronger among women aged <35 years, lived in urban regions, or measured AMH in cold-season (P for interaction <0.05). CONCLUSION: PM2.5 and specific chemical components (particularly NH4+, NO3-, and SO42-) exposure during the secondary to antral follicle stage and 1-year before measurement were associated with diminished ovarian reserve (DOR), indicating the adverse impact of PM2.5 and its constituent exposures on female reproductive potential.


Subject(s)
Air Pollutants , Air Pollution , Ovarian Reserve , Female , Humans , Particulate Matter/analysis , Retrospective Studies , Air Pollution/analysis , Fertility , Anti-Mullerian Hormone , China , Air Pollutants/analysis , Environmental Exposure
15.
bioRxiv ; 2023 Aug 02.
Article in English | MEDLINE | ID: mdl-37577682

ABSTRACT

The TMEM16A calcium-activated chloride channel is a promising therapeutic target for various diseases. Niclosamide, an anthelmintic medication, has been considered as a TMEM16A inhibitor for treating asthma and chronic obstructive pulmonary disease, but was recently found to possess broad-spectrum off-target effects. Here we show that, under physiological conditions, niclosamide acutely potentiates TMEM16A without having any inhibitory effect. Our computational and functional characterizations pinpoint a putative niclosamide binding site on the extracellular side of TMEM16A. Mutations in this site attenuate the potentiation. Moreover, niclosamide potentiates endogenous TMEM16A in vascular smooth muscle cells, triggers intracellular calcium increase, and constricts the murine mesenteric artery. Our findings advise caution when considering niclosamide as a TMEM16A inhibitor to treat diseases such as asthma, COPD, and hypertension. The identification of the putative niclosamide binding site provides insights into the mechanism of TMEM16A pharmacological modulation, shining light on developing specific TMEM16A modulators to treat human diseases.

16.
Clin Lab ; 69(8)2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37560870

ABSTRACT

BACKGROUND: This study aimed to investigate the value of miR-671-5p in multiple myeloma (MM) in diagnostics and prognosis and developed a potential biomarker to improve the prognosis of MM. METHODS: Plasma cells were isolated from bone marrow samples of 80 MM patients, in which miR-671-5p levels were determined. The correlation between miR-671-5p expression with serum creatinine, ß-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, chromosomal abnormalities, and albumin was analyzed. The association between miR-671-5p expression with progression-free survival and overall survival in MM patients was determined. RESULTS: miR-671-5p expression was reduced and predicted an increased risk of MM. miR-671-5p expression was negatively correlated with serum creatinine, ß-2-microglobulin, lactate dehydrogenase, bone lesions, International Staging System staging, and chromosomal abnormalities, and positively correlated with albumin. miR-671-5p expression was augmented in complete response patients and overall response rate patients, and differentiated CR and ORR patients from Non-CR and Non-ORR patients. Furthermore, miR-671-5p low expression was associated with unfavorable progression-free survival and overall survival in MM patients. CONCLUSIONS: In a word, miR-671-5p is associated with worsening clinical properties, increased ISS staging, unfavorable chromosomal abnormalities, and poor prognosis in MM patients.


Subject(s)
MicroRNAs , Multiple Myeloma , Humans , MicroRNAs/genetics , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Creatinine , Prognosis , Albumins , Chromosome Aberrations , Lactate Dehydrogenases
17.
Front Public Health ; 11: 1159348, 2023.
Article in English | MEDLINE | ID: mdl-37457253

ABSTRACT

Background: Noise energy has been well-established to increase the risk of occupational noise-induced hearing loss (NIHL). However, the role of noise temporal structure (expressed by kurtosis) or its combination with energy metrics (e.g., kurtosis-adjusted cumulative noise exposure, adj-CNE) in occupational NIHL was still unclear. Methods: A cross-sectional survey of 867 Chinese workers, including 678 metal manufacturing workers and 189 workers exposed to Gaussian noise, was conducted. Noise energy metrics, including LAeq,8h and CNE, kurtosis (ß), and adj-CNE were used to quantify noise exposure levels. Noise-induced permanent threshold shift at frequencies 3, 4, and 6 kHz (NIPTS346) and the prevalence of high-frequency NIHL (HFNIHL%) were calculated for each participant. The dose-response relationship between kurtosis or adj-CNE and occupational NIHL was observed. Results: Among 867 workers, different types of work had specific and independent noise energy and kurtosis values (p > 0.05). HFNIHL% increased with an increase in exposure duration (ED), LAeq,8h, CNE, or kurtosis (p < 0.01), and there were strong linear relationships between HFNIHL% and ED (coefficient of determination [R2] = 0.963), CNE (R2 = 0.976), or kurtosis (R2 = 0.938, when CNE < 100 dB(A)∙year). The "V" shape notching extent in NIPTS became deeper with increasing kurtosis when CNE < 100 dB(A)∙year and reached the notching bottom at the frequency of 4 or 6 kHz. The workers exposed to complex noise (ß ≥ 10) had a higher risk of NIHL than those exposed to Gaussian noise (ß < 10) at the frequencies of 3, 4, 6, and 8 kHz (OR > 2, p < 0.01). Moreover, HFNIHL% increased with adj-CNE (p < 0.001). There were strong linear relationships between NIHL and adj-CNE or CNE when ß ≥ 10 (R2adj-CNE > R2CNE). After CNE was adjusted by kurtosis, average differences in NIPTS346 or HFNIHL% between the complex and Gaussian noise group were significantly reduced (p < 0.05). Conclusion: Kurtosis was a key factor influencing occupational NIHL among metal manufacturing workers, and its combination with energy metrics could assess the risk of NIHL more effectively than CNE alone.


Subject(s)
Hearing Loss, Noise-Induced , Noise, Occupational , Occupational Exposure , Humans , Hearing Loss, Noise-Induced/epidemiology , Hearing Loss, Noise-Induced/etiology , Occupational Exposure/adverse effects , Cross-Sectional Studies , Surveys and Questionnaires , Noise, Occupational/adverse effects
18.
Ann Diagn Pathol ; 66: 152165, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37348414

ABSTRACT

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous group of non-Hodgkin lymphoma, characterized by a variety of clinicopathological, histomorphological, immunophenotypic, and molecular genetic features. The subtype of DLBCL known as double-expressor lymphoma (DEL) is associated with an adverse prognosis when treated with R-CHOP. Our study aimed to investigate the clinicopathologic features of DEL and the prognostic roles of Myc rearrangement and C-Myc expression in DEL patients. PATIENTS AND METHODS: We conducted a retrospective study of 145 patients who were identified through fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) testing. RESULTS: We found that DEL patients were more likely to have a non-germinal center B-cell (GCB) subtype, stage III/IV disease, and a high International Prognostic Index (IPI) score. Our survival analysis indicated that Myc rearrangement and C-Myc expression were associated with poor prognosis. Although DEL patients with Myc rearrangement exhibited trends towards worse survival compared with patients without Myc rearrangement, the differences were not statistically significant (P = 0.4008). The median overall survival (OS) of DEL patients with ≥70 % C-Myc expression (DEL-C-Mychigh) was 5 months. In the DEL-C-Mychigh group, the non-GCB subtype showed nonsignificant trends towards poorer survival compared with the GCB subtype (P = 0.1042). CONCLUSION: In conclusion, our study shows that a cut-off of ≥70 % for C-Myc expression in DEL patients can improve risk stratification, and suggests that more intensive treatment regimens may be necessary to improve survival in this high-risk population.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Proto-Oncogene Proteins c-myc , Humans , Retrospective Studies , In Situ Hybridization, Fluorescence , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
19.
Org Lett ; 25(20): 3607-3610, 2023 May 26.
Article in English | MEDLINE | ID: mdl-37166363

ABSTRACT

An enantioselective metal-free hydrogenation of hydrazones has been realized successfully using chiral boranes as catalysts, producing a range of optically active hydrazines in 87-99% yields with 75-93% ee's. The bulky 2,2,6,6-tetramethylpiperidinyl moiety was found to be essential for achieving the high enantioselectivities.

20.
Photoacoustics ; 31: 100494, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37131996

ABSTRACT

Membrane viscosity is an important property of cell biology, which determines cellular function, development and disease progression. Various experimental and computational methods have been developed to investigate the mechanics of cells. However, there have been no experimental measurements of the membrane viscosity at high-frequencies in live cells. High frequency measurements are important because they can probe viscoelastic effects. Here, we investigate the membrane viscosity at gigahertz-frequencies through the damping of the acoustic vibrations of gold nanoplates. The experiments are modeled using a continuum mechanics theory which reveals that the membranes display viscoelasticity, with an estimated relaxation time of ca. 5.7 + 2.4 / - 2.7 ps. We further demonstrate that membrane viscoelasticity can be used to differentiate a cancerous cell line (the human glioblastoma cells LN-18) from a normal cell line (the mouse brain microvascular endothelial cells bEnd.3). The viscosity of cancerous cells LN-18 is lower than that of healthy cells bEnd.3 by a factor of three. The results indicate promising applications of characterizing membrane viscoelasticity at gigahertz-frequency in cell diagnosis.

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