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1.
Arch Microbiol ; 206(3): 131, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38421449

RESUMO

A new strain of Bacillus velezensis NDB was isolated from Xiangshan Harbor and antibacterial test revealed antibacterial activity of this strain against 12 major pathogenic bacteria. The whole genome of the bacterium was sequenced and found to consist of a 4,214,838 bp circular chromosome and a 7410 bp circular plasmid. Furthermore, it was predicted by AntiSMASH and BAGEL4 to have 12 clusters of secondary metabolism genes for the synthesis of the inhibitors, fengycin, bacillomycin, macrolactin H, bacillaene, and difficidin, and there were also five clusters encoding potentially novel antimicrobial substances, as well as three bacteriocin biosynthesis gene clusters of amylocyclicin, ComX1, and LCI. qRT-PCR revealed significant up-regulation of antimicrobial secondary metabolite synthesis genes after 24 h of antagonism with pathogenic bacteria. Furthermore, MALDI-TOF mass spectrometry revealed that it can secrete surfactin non-ribosomal peptide synthase and polyketide synthase to exert antibacterial effects. GC-MS was used to analyze methanol extract of B. velezensis NDB, a total of 68 compounds were identified and these metabolites include 16 amino acids, 17 acids, 3 amines, 11 sugars, 11 alcohols, 1 ester, and 9 other compounds which can inhibit pathogenic bacteria by initiating the antibiotic secretion pathway. A comparative genomic analysis of gene families showed that the specificity of B. velezensis NDB was mainly reflected in environmental adaptability. Overall, this research on B. velezensis NDB provides the basis for elucidating its biocontrol effect and promotes its future application as a probiotic.


Assuntos
Bacillus , Bacillus/genética , Antibacterianos/farmacologia , Aminas , Aminoácidos
2.
Eur J Pharmacol ; 967: 176355, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38280463

RESUMO

Pulmonary fibrosis is a challenging lung disease characterized by a bleak prognosis. A pivotal element in the progression of this disease is the dysregulated recruitment of macrophages. Nicotinamide phosphoribose transferase (NAMPT), secreted by alveolar epithelial cells and inflammatory cells, has been previously identified to influence macrophage inflammation in acute lung injury through the nicotinamide adenine dinucleotide (NAD) rescue synthesis pathway. Nonetheless, the exact role of NAMPT in the regulation of lung fibrosis is yet to be elucidated. In our research, we employed bleomycin (BLM) to induce pulmonary fibrosis in Namptflox/flox;Cx3cr1CreER mice, using Namptflox/flox mice as controls. Our findings revealed an augmented expression of NAMPT concurrent with a marked increase in the secretion of NAD and inflammatory cytokines such as IL-6, TNF-α, and TGF-ß1 post-BLM treatment. Furthermore, an upsurge in NAMPT-positive macrophages was observed in the lungs of BLM-treated Namptflox/flox mice. Notably, a conditional knockout of NAMPT (NAMPT cKO) in lung macrophages curtailed the BLM-induced inflammatory responses and significantly mitigated pulmonary fibrosis. This was associated with diminished phospho-Sirt1 (p-Sirt1) expression levels and a concomitant rise in mothers against decapentaplegic homolog 7 (Smad7) expression in BLM-treated mouse lungs and murine RAW 264.7 macrophage cells. Collectively, our data suggests that NAMPT exacerbates macrophage-driven inflammation and pulmonary fibrosis via the Sirt1-Smad7 pathway, positioning NAMPT as a promising therapeutic target for pulmonary fibrosis intervention.


Assuntos
Fibrose Pulmonar , Animais , Camundongos , Bleomicina/efeitos adversos , Citocinas/metabolismo , Inflamação , Macrófagos/metabolismo , NAD , Niacinamida , Nicotinamida Fosforribosiltransferase/genética , Fibrose Pulmonar/induzido quimicamente , Sirtuína 1/genética , Sirtuína 1/metabolismo , Transferases
3.
Clin Transl Med ; 14(1): e1521, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38279895

RESUMO

BACKGROUND: One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients. METHODS: We collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy. RESULTS: In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. CONCLUSION: Targeting one-carbon metabolism is useful for cancer immunotherapy.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Antineoplásicos/uso terapêutico , Redes e Vias Metabólicas , Carbono/metabolismo , Carbono/uso terapêutico
4.
Asian J Surg ; 47(4): 1734-1739, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38185563

RESUMO

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.


Assuntos
Neoplasias da Glândula Tireoide , Tireoidectomia , Humanos , Deglutição , Músculos do Pescoço/patologia , Endoscopia , Esvaziamento Cervical , Neoplasias da Glândula Tireoide/cirurgia
5.
Front Bioeng Biotechnol ; 11: 1302524, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38047288

RESUMO

Accurate 3D localization of the mandibular canal is crucial for the success of digitally-assisted dental surgeries. Damage to the mandibular canal may result in severe consequences for the patient, including acute pain, numbness, or even facial paralysis. As such, the development of a fast, stable, and highly precise method for mandibular canal segmentation is paramount for enhancing the success rate of dental surgical procedures. Nonetheless, the task of mandibular canal segmentation is fraught with challenges, including a severe imbalance between positive and negative samples and indistinct boundaries, which often compromise the completeness of existing segmentation methods. To surmount these challenges, we propose an innovative, fully automated segmentation approach for the mandibular canal. Our methodology employs a Transformer architecture in conjunction with cl-Dice loss to ensure that the model concentrates on the connectivity of the mandibular canal. Additionally, we introduce a pixel-level feature fusion technique to bolster the model's sensitivity to fine-grained details of the canal structure. To tackle the issue of sample imbalance and vague boundaries, we implement a strategy founded on mandibular foramen localization to isolate the maximally connected domain of the mandibular canal. Furthermore, a contrast enhancement technique is employed for pre-processing the raw data. We also adopt a Deep Label Fusion strategy for pre-training on synthetic datasets, which substantially elevates the model's performance. Empirical evaluations on a publicly accessible mandibular canal dataset reveal superior performance metrics: a Dice score of 0.844, click score of 0.961, IoU of 0.731, and HD95 of 2.947 mm. These results not only validate the efficacy of our approach but also establish its state-of-the-art performance on the public mandibular canal dataset.

6.
bioRxiv ; 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38076853

RESUMO

The human airway contains specialized rare epithelial cells whose roles in respiratory disease are not well understood. Ionocytes express the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), while chemosensory tuft cells express asthma-associated alarmins. However, surprisingly, exceedingly few mature tuft cells have been identified in human lung cell atlases despite the ready identification of rare ionocytes and neuroendocrine cells. To identify human rare cell progenitors and define their lineage relationship to mature tuft cells, we generated a deep lung cell atlas containing 311,748 single cell RNA-Seq (scRNA-seq) profiles from discrete anatomic sites along the large and small airways and lung lobes of explanted donor lungs that could not be used for organ transplantation. Of 154,222 airway epithelial cells, we identified 687 ionocytes (0.45%) that are present in similar proportions in both large and small airways, suggesting that they may contribute to both large and small airways pathologies in CF. In stark contrast, we recovered only 3 mature tuft cells (0.002%). Instead, we identified rare bipotent progenitor cells that can give rise to both ionocytes and tuft cells, which we termed tuft-ionocyte progenitor cells (TIP cells). Remarkably, the cycling fraction of these TIP cells was comparable to that of basal stem cells. We used scRNA-seq and scATAC-seq to predict transcription factors that mark this novel rare cell progenitor population and define intermediate states during TIP cell lineage transitions en route to the differentiation of mature ionocytes and tuft cells. The default lineage of TIP cell descendants is skewed towards ionocytes, explaining the paucity of mature tuft cells in the human airway. However, Type 2 and Type 17 cytokines, associated with asthma and CF, diverted the lineage of TIP cell descendants in vitro , resulting in the differentiation of mature tuft cells at the expense of ionocytes. Consistent with this model of mature tuft cell differentiation, we identify mature tuft cells in a patient who died from an asthma flare. Overall, our findings suggest that the immune signaling pathways active in asthma and CF may skew the composition of disease-relevant rare cells and illustrate how deep atlases are required for identifying physiologically-relevant scarce cell populations.

8.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 40(6): 1175-1184, 2023 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-38151941

RESUMO

Soft tissue defects resulting from head and neck tumor resection seriously impact the physical appearance and psychological well-being of patients. The complex curvature of the human head and neck poses a formidable challenge for maxillofacial surgeons to achieve precise aesthetic and functional restoration after surgery. To this end, a normal head and neck volunteer was selected as the subject of investigation. Employing Gaussian curvature analysis, combined with mechanical constraints and principal curvature analysis methods of soft tissue clinical treatment, a precise developable/non-developable area partition map of the head and neck surface was obtained, and a non-developable surface was constructed. Subsequently, a digital design method was proposed for the repair of head and neck soft tissue defects, and an in vitro simulated surgery experiment was conducted. Clinical verification was performed on a patient with tonsil tumor, and the results demonstrated that digital technology-designed flaps improved the accuracy and aesthetic outcome of head and neck soft tissue defect repair surgery. This study validates the feasibility of digital precision repair technology for soft tissue defects after head and neck tumor resection, which effectively assists surgeons in achieving precise flap transplantation reconstruction and improves patients' postoperative satisfaction.


Assuntos
Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Humanos , Retalhos Cirúrgicos/cirurgia , Neoplasias de Cabeça e Pescoço/cirurgia , Cabeça/cirurgia , Pescoço/cirurgia
9.
J Dent ; 138: 104727, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37769934

RESUMO

OBJECTIVES: This article reviews recent advances in computer-aided segmentation methods for oral and maxillofacial surgery and describes the advantages and limitations of these methods. The objective is to provide an invaluable resource for precise therapy and surgical planning in oral and maxillofacial surgery. Study selection, data and sources: This review includes full-text articles and conference proceedings reporting the application of segmentation methods in the field of oral and maxillofacial surgery. The research focuses on three aspects: tooth detection segmentation, mandibular canal segmentation and alveolar bone segmentation. The most commonly used imaging technique is CBCT, followed by conventional CT and Orthopantomography. A systematic electronic database search was performed up to July 2023 (Medline via PubMed, IEEE Xplore, ArXiv, Google Scholar were searched). RESULTS: These segmentation methods can be mainly divided into two categories: traditional image processing and machine learning (including deep learning). Performance testing on a dataset of images labeled by medical professionals shows that it performs similarly to dentists' annotations, confirming its effectiveness. However, no studies have evaluated its practical application value. CONCLUSION: Segmentation methods (particularly deep learning methods) have demonstrated unprecedented performance, while inherent challenges remain, including the scarcity and inconsistency of datasets, visible artifacts in images, unbalanced data distribution, and the "black box" nature. CLINICAL SIGNIFICANCE: Accurate image segmentation is critical for precise treatment and surgical planning in oral and maxillofacial surgery. This review aims to facilitate more accurate and effective surgical treatment planning among dental researchers.


Assuntos
Cirurgia Bucal , Dente , Radiografia Panorâmica , Processamento de Imagem Assistida por Computador/métodos , Artefatos
10.
Head Neck ; 45(9): 2394-2412, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37417818

RESUMO

BACKGROUND: This paper aims to analyze the time trend of OCs incidence in 43 countries (1988-2012) and predict the incidence trend of OCs (2012-2030). METHODS: In the database for Cancer Incidence in Five Continents, the annual data on OCs incidence grouped by age and gender were obtained from 108 cancer registries in 43 countries. The age-standardized incidence rates were calculated, and the Bayesian age-period-cohort model was used to predict the incidence in 2030. RESULTS: South Asia and Oceania had the highest ASR in 1988 (9.24/100 000) and 2012 (6.74/100 000). It was predicted that India, Thailand, the United Kingdom, the Czech Republic, Austria, and Japan would be the countries with an increased incidence of OCs in 2030. CONCLUSION: Regional custom is an important factor affecting the incidence of OCs. According to our predictions., it is necessary to control risk factors according to local conditions and enhance screening and education.


Assuntos
Neoplasias Bucais , Humanos , Incidência , Teorema de Bayes , Neoplasias Bucais/epidemiologia , Japão/epidemiologia , Fatores de Risco , Sistema de Registros
11.
Clin Exp Med ; 23(8): 4825-4834, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37306872

RESUMO

Thyroid cancer is the endocrine tumor with the highest incidence at present. It originates from the thyroid follicular epithelium or follicular paraepithelial cells. There is an increasing incidence of thyroid cancer all over the world. We found that SRPX2 expression level was higher in papillary thyroid tumors than in normal thyroid tissues, and SRPX2 expression was closely related to tumor grade and clinical prognosis. Previous reports showed that SRPX2 could function by activating PI3K/AKT signaling pathway. In addition, in vitro experiments showed that SRPX2 promoted the proliferation and migration of papillary thyroid cancer (PTC). In conclusion, SRPX2 could promote the malignant development of PTC. This may be a potential treatment target for PTC.


Assuntos
Fosfatidilinositol 3-Quinases , Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia
12.
Gland Surg ; 12(5): 664-676, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37284705

RESUMO

Background: The increase in the diagnosis of papillary thyroid carcinoma (PTC) has prompted researchers to establish a diagnostic model and identify functional subclusters. The Human Phenotype Ontology (HPO) platform is widely available for differential diagnostics and phenotype-driven investigations based on next-generation sequence-variation data. However, a systematic and comprehensive study to identify and validate PTC subclusters based on HPO is lacking. Methods: We first used the HPO platform to identify the PTC subclusters. An enrichment analysis was then conducted to examine the key biological processes and pathways associated with the subclusters, and a gene mutation analysis of the subclusters was conducted. For each subcluster, the differentially expressed genes (DEGs) were selected and validated. Finally, a single-cell RNA-sequencing data set was used to verify the DEGs. Results: In our study, 489 PTC patients from The Cancer Genome Atlas (TCGA) were included. Our analysis demonstrated that distinct subclusters of PTC are associated with different survival times and have different functional enrichment, and that C-C motif chemokine ligand 21 (CCL21) and zinc finger CCHC-type containing 12 (ZCCHC12) were the common down- and upregulated genes, respectively, in the 4 subclusters. Additionally, 20 characteristic genes were identified in the 4 subclusters, some of which have previously been reported to have roles in PTC. Further, we found that these characteristic genes were mainly expressed in thyrocytes, endothelial cells, and fibroblasts, and were rarely expressed in immune cells. Conclusions: We first identified subclusters in PTC based on HPO and found that patients with distinct subclusters have different prognoses. We then identified and validated the characteristic genes in the 4 subclusters. These findings are expected to serve as a crucial reference that will improve our understanding of PTC heterogeneity and the use of novel targets.

13.
Cogn Process ; 24(3): 451-462, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36952054

RESUMO

The relationship between self-reported sleep and cognitive function is complex; it is unclear whether self-reported sleep is a robust correlate of people's cognitive function. We address this gap by using a comprehensive large-scale dataset (N = 1054) coupled with a novel modeling approach, specification curve analysis (SCA), to test the association between self-reported sleep and cognitive function. The results of the SCA showed robust correlations between self-reported sleep and cognitive function, with poorer sleep associated with worse cognitive function. Furthermore, the correlations between sleep components and cognitive function were heterogeneous, with differences emerging across cognitive measures and domains. Specifically, daytime dysfunction was associated with the strongest effect on subjective cognitive function, whereas sleep duration and sleep efficiency had the strongest effect on objective cognitive function. Therefore, the relationship between self-reported sleep and cognition depends largely on what and how cognitive function is measured. Our findings guide measurement and domain selection for future research on the role of sleep in cognitive function.


Assuntos
Cognição , Sono , Humanos , Autorrelato , Duração do Sono
14.
Comp Med ; 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36922006

RESUMO

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing cancer models, minimally invasive methods of intrapleural injection are desirable because inflammation at the injection site can have a major impact on tumor growth and progression. Common approaches for intrapleural injection include surgical exposure of the thoracic wall or the diaphragm prior to injection; however, these invasive procedures require tissue dissection that triggers an undesirable inflammatory response and increases the risk of pneumothorax. While nonsurgical procedures can minimize this concern, 'blind' injections may lead to off target inoculation. In this study, we hypothesized that a minimally invasive transthoracic approach (MI-TT) would produce a tumor distribution and burden similar to that of a surgical transabdominal approach (SX-TA). Prior to performing the procedures on live mice, surgeons were trained using cadavers and terminal procedures. Then a total of 14 nude mice (female, 4 to 6 wk old) were injected with 50 µL (5 million) A549-Luc2 human cancer cells either using the MI-TT (n = 8) or SX-TA (n = 6) approach under carprofen analgesia and isoflurane anesthesia. Our results indicate that with training, a minimally invasive transthoracic approach for intrapleural injection provides more consistent tumor placement and a greater tumor burden than does the surgical method. However, additional studies are necessary to confirm anatomic placement and characterize tumor profiles.

15.
Elife ; 122023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36994985

RESUMO

The specific functional properties of a tissue are distributed amongst its component cell types. The various cells act coherently, as an ensemble, in order to execute a physiologic response. Modern approaches for identifying and dissecting novel physiologic mechanisms would benefit from an ability to identify specific cell types in live tissues that could then be imaged in real time. Current techniques require the use of fluorescent genetic reporters that are not only cumbersome, but which only allow the study of three or four cell types at a time. We report a non-invasive imaging modality that capitalizes on the endogenous autofluorescence signatures of the metabolic cofactors NAD(P)H and FAD. By marrying morphological characteristics with autofluorescence signatures, all seven of the airway epithelial cell types can be distinguished simultaneously in mouse tracheal explants in real time. Furthermore, we find that this methodology for direct cell type-specific identification avoids pitfalls associated with the use of ostensibly cell type-specific markers that are, in fact, altered by clinically relevant physiologic stimuli. Finally, we utilize this methodology to interrogate real-time physiology and identify dynamic secretory cell associated antigen passages (SAPs) that form in response to cholinergic stimulus. The identical process has been well documented in the intestine where the dynamic formation of SAPs and goblet cell associated antigen passages (GAPs) enable luminal antigen sampling. Airway secretory cells with SAPs are frequently juxtaposed to antigen presenting cells, suggesting that airway SAPs, like their intestinal counterparts, not only sample antigen but convey their cargo for immune cell processing.


Imaging several cell types, at the same time, within a living tissue is no small endeavor. To do so, scientists usually have to perform genetic manipulations that make certain proteins in each cell type fluorescent and therefore easy to track. However, these approaches are cumbersome, limited, and often not applicable to intact human tissues. A possible alternative would be to make use of autofluorescence ­ the fact that certain molecules in living cells naturally fluoresce when exposed to a particular wavelength of light. For example, this is the case for NAD(P)H and FAD, two small molecules necessary for life's biochemical processes, and whose intracellular levels and locations vary depending on cell type. In response, Shah, Hou et al. developed a new imaging technique that takes advantage of the unique autofluorescence signatures of NAD(P)H and FAD to distinguish between the seven different types of cells that line the surface of the airways of mice. Using their autofluorescence approach, Shah, Hou et al. were also able to discover a new role for secretory cells, which normally produce fluids, mucus and various proteins necessary for the lungs to work properly. The imaging experiments show that these cells could also sample material from the surface of the airway in a manner similar to how cells in the intestine take up material from the gut and pass their cargo to immune cells that mediate infection control or tolerance. Further studies should uncover more details about this new function of secretory lung cells. Other exciting discoveries may also emerge from researchers adopting the method developed by Shah, Hou et al. to examine a range of organs (both healthy and diseased), and attempting to apply it to human tissues.


Assuntos
Antígenos , Células Caliciformes , Camundongos , Animais , Células Apresentadoras de Antígenos , Fagocitose , Imagem Óptica
16.
Comp Med ; 73(1): 91-103, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36744556

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the worldwide coronavirus (COVID-19) pandemic, has infected an estimated 525 million people with over 6 million deaths. Although COVID-19 is primarily a respiratory disease, an escalating number of neurologic symptoms have been reported in humans. Some neurologic symptoms, such as loss of smell or taste, are mild. However, other symptoms, such as meningoencephalitis or stroke, are potentially fatal. Along with surveys and postmortem evaluations on humans, scientists worked with several animal species to try to elucidate the causes of neurologic symptoms. Neurologic sequelae remain challenging to study due to the complexity of the nervous system and difficulties in identification and quantification of neurologic signs. We reviewed animal models used in the study of neurologic COVID-19, specifically research in mice, hamsters, ferrets, and nonhuman primates. We summarized findings on the presence and pathologic effects of SARS-CoV-2 on the nervous system. Given the need to increase understanding of COVID-19 and its effects on the nervous system, scientists must strive to obtain new information from animals to reduce mortality and morbidity with neurologic complications in humans.


Assuntos
COVID-19 , Doenças do Sistema Nervoso , Humanos , Animais , Camundongos , SARS-CoV-2 , Furões , Doenças do Sistema Nervoso/diagnóstico , Modelos Animais
17.
Drug Resist Updat ; 68: 100939, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36806005

RESUMO

Thyroid cancer is the most prevalent endocrine tumor and its incidence is fast-growing worldwide in recent years. Differentiated thyroid cancer (DTC) is the most common pathological subtype which is typically curable with surgery and Radioactive iodine (RAI) therapy (approximately 85%). Radioactive iodine is the first-line treatment for patients with metastatic Papillary Thyroid Cancer (PTC). However, 60% of patients with aggressive metastasis DTC developed resistance to RAI treatment and had a poor overall prognosis. The molecular mechanisms of RAI resistance include gene mutation and fusion, failure to transport RAI into the DTC cells, and interference with the tumor microenvironment (TME). However, it is unclear whether the above are the main drivers of the inability of patients with DTC to benefit from iodine therapy. With the development of new biological technologies, strategies that bolster RAI function include TKI-targeted therapy, DTC cell redifferentiation, and improved drug delivery via extracellular vesicles (EVs) have emerged. Despite some promising data and early success, overall survival was not prolonged in the majority of patients, and the disease continued to progress. It is still necessary to understand the genetic landscape and signaling pathways leading to iodine resistance and enhance the effectiveness and safety of the RAI sensitization approach. This review will summarize the mechanisms of RAI resistance, predictive biomarkers of RAI resistance, and the current RAI sensitization strategies.


Assuntos
Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/radioterapia , Radioisótopos do Iodo/uso terapêutico , Biomarcadores , Transdução de Sinais , Microambiente Tumoral/genética
18.
Ageing Res Rev ; 86: 101885, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36801378

RESUMO

Cerebral small vessel diseases (CSVD) consist of a group of diseases with high heterogeneity induced by pathologies of intracranial small blood vessels. Endothelium dysfunction, bloodbrain barrier leakage and the inflammatory response are traditionally considered to participate in the pathogenesis of CSVD. However, these features cannot fully explain the complex syndrome and related neuroimaging characteristics. In recent years, the glymphatic pathway has been discovered to play a pivotal role in clearing perivascular fluid and metabolic solutes, which has provided novel insights into neurological disorders. Researchers have also explored the potential role of perivascular clearance dysfunction in CSVD. In this review, we presented a brief overview of CSVD and the glymphatic pathway. In addition, we elucidated CSVD pathogenesis from the perspective of glymphatic failure, including basic animal models and clinical neuroimaging markers. Finally, we proposed forthcoming clinical applications targeting the glymphatic pathway, hoping to provide novel ideas on promising therapies and preventions of CSVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Sistema Glinfático , Doenças do Sistema Nervoso , Animais , Humanos , Sistema Glinfático/patologia , Barreira Hematoencefálica , Neuroimagem/efeitos adversos , Doenças do Sistema Nervoso/patologia , Biomarcadores , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/etiologia , Imageamento por Ressonância Magnética
19.
J Am Assoc Lab Anim Sci ; 62(1): 48-54, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36755204

RESUMO

Sanitation guidelines for animal research facilities state that disinfection is achieved by application of high-temperature water (143 to 180 °F [62 to 82 °C]) or detergents and disinfectants. However, these guidelines are based on requirements for pasteurization, which may be unnecessarily stringent for the sanitation of nonfood items and do not address the theoretical sanitation potential of water at temperatures below 143 °F (62 °C). Recent literature indicates that water temperatures below 143 °F (62 °C) can also provide effective sanitation. In this study, we compared cagewash cycles at low (100 °F [38 °C] and 120 °F [49 °C]) and high (standard) (180 °F [82 °C]) temperatures and evaluated sanitation efficacy by using ATP swabs and RODAC plates. Low-temperature loads were washed either with or without prior treatment of a chemical disinfectant (10% bleach). The 100 °F (38 °C) cycle was not sufficient for sanitization without bleach pretreatment. However, the 120 °F (49 °C) cycle effectively sanitized cages without bleach pretreatment. Validation of effective sanitation at a lower water temperature (120 °F [49 °C]) can improve cagewash logistics and reduce costs as compared with standard (180 °F [82 °C]) high-temperature cycles.


Assuntos
Desinfetantes , Habitação , Animais , Temperatura , Roedores , Saneamento , Água
20.
Water Res ; 230: 119527, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36580800

RESUMO

Production of medium-chain carboxylic acids (MCCAs) by chain elongation (CE) presents a competitive alternative to conventional products of methane in anaerobic digestion treating organic waste streams, considering energy recovery, economic, and environmental profits. However, the system stability and performance largely rely on the selective suppression of methanogens while stimulation of CE bacteria. Commercial inhibitors such as 2-bromoethanesulfonic sodium (BES) was shown to be effective, but controversial conclusions exist on its inhibition characteristics and the inhibition mechanism remains unclear. Therefore, this study systematically investigated the responses of methanogenesis in granular sludge to various BES levels, focusing on methane production, methanogenic pathway, dynamic populations, electron transport and energy metabolism. Results showed that compared with the control, 3.0 g/L BES was sufficient to induce a 72.9% reduced level on accumulative methane production by the end of 4 cycles (28 days), which was likely to be attributed to the significantly suppressed metabolic pathways and intracellular regulations. Specifically, BES suppressed the electron transport via unproper electron carriers and reduced electron amount as indicated by the decreased level of enzymes and genes involved such as coenzyme F420, CO dehydrogenase and NADH:ubiquinone reductase (H+-translocating). Moreover, BES regulated the intracellular energy metabolism, leading to the impeded ATP synthesis but enhanced ATP consumption as evidenced by the variations on the activity or abundance of acetate kinase, A1Ao-ATP synthase, nitrogenase and ATP citrate synthase. Additionally, BES enriched hydrogenotrophic methanogenesis over acetoclastic one as supported by variations on the archaeal community structures and regulations of differentially expressed genes involved. Moreover, BES also reduced the contents of both protein and carbohydrate in extracellular polymeric substances (EPS). This study is expected to enhance understanding of BES contribution to methanogenesis inhibition but MCCAs production in CE bioreactors.


Assuntos
Ácidos Alcanossulfônicos , Bactérias , Bactérias/metabolismo , Anaerobiose , Esgotos/química , Trifosfato de Adenosina/metabolismo , Metano/metabolismo , Reatores Biológicos/microbiologia
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