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1.
Folia Med Cracov ; 64(2): 63-68, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39324678

RESUMO

The median sacral artery (MSA) is the single unpaired dorsal branch of the abdominal aorta. The present case describes the relatively unusual origin of the median sacral artery in common with the fourth pair of lumbar arteries via a common trunk in a 74-year-old males' cadaver. Unusual common trunk is prone for iatrogenic injury in surgeries of the lumbar and pelvic region. Owing to the deep seated nature of MSA close to the periosteum of lumbar vertebrae and sacrum, detection of accidental rupture of MSA and ligation thereof becomes a difficult task. MSA is also increasingly being utilized for intra-arterial embolization of pelvic tumours. The proximal portion of the common origin may at times undergo cone shaped dilatation which is referred to as infundibulum or infundibular dilatation and can also transform into aneurysm later. Knowledge of this variation is imperative for spine and pelvic surgeons to avoid unwanted complications.


Assuntos
Vértebras Lombares , Sacro , Humanos , Masculino , Idoso , Sacro/irrigação sanguínea , Vértebras Lombares/irrigação sanguínea , Aorta Abdominal , Cadáver , Região Lombossacral/irrigação sanguínea
2.
J Biol Chem ; : 107753, 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39260692

RESUMO

Chronic stress can have adverse consequences on human health by disrupting the hormonal balance in our body. Earlier, we observed elevated levels of cortisol, a primary stress hormone, and some exosomal microRNAs in the serum of breast cancer patients. Here, we investigated the role of cortisol in microRNA induction and its functional consequences. We found that cortisol induced the expression of miR-143/145 cluster in human monocyte (THP1 and U937)-derived macrophages but not in breast cancer cells. In silico analysis identified glucocorticoid-response element in the upstream CARMN promoter utilized by the miR-143/145 cluster. Enhanced binding of glucocorticoid-receptor (GR) upon cortisol exposure and its regulatory significance was confirmed by chromatin-immunoprecipitation and promoter-reporter assays. Further, cortisol inhibited IFNγ-induced M1 polarization and promoted M2 polarization, and these effects were suppressed by miR-143-3p and miR-145-5p inhibitors pretreatment. Cortisol-treated macrophages exhibited increased oxygen-consumption rate (OCR) to extracellular-acidification rate (ECAR) ratio, and this change was neutralized by functional inhibition of miR-143-3p and miR-145-5p. HK2 and ADPGK were confirmed as the direct targets of miR-143-3p and miR-145-5p, respectively. Interestingly, silencing of HK2 and ADPGK inhibited IFNγ-induced M1 polarization, but failed to induce M2 polarization, since it suppressed both ECAR and OCR, while OCR was largely sustained in cortisol-treated M2-polarized macrophages. We found that cortisol treatment sustained OCR by enhancing fatty acid and glutamine metabolism through upregulation of CPT2 and GLS, respectively, to support M2 polarization. Thus, our findings unfold a novel mechanism of immune suppression by cortisol and open avenues for preventive and therapeutic interventions.

3.
Sci Transl Med ; 16(764): eadi0284, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259813

RESUMO

Proinflammatory hepatic macrophage activation plays a key role in the development of nonalcoholic steatohepatitis (NASH). This involves increased embryonic hepatic Kupffer cell (KC) death, facilitating the replacement of KCs with bone marrow-derived recruited hepatic macrophages (RHMs) that highly express proinflammatory genes. Moreover, phago/efferocytic activity of KCs is diminished in NASH, enhancing liver inflammation. However, the molecular mechanisms underlying these changes in KCs are not known. Here, we show that hypoxia-inducible factor 2α (HIF-2α) mediates NASH-associated decreased KC growth and efferocytosis by enhancing lysosomal stress. At the molecular level, HIF-2α stimulated mammalian target of rapamycin (mTOR)- and extracellular signal-regulated kinase-dependent inhibitory transcription factor EB (TFEB) phosphorylation, leading to decreased lysosomal and phagocytic gene expression. With increased metabolic stress and phago/efferocytic burden in NASH, these changes were sufficient to increase lysosomal stress, causing decreased efferocytosis and lysosomal cell death. Of interest, HIF-2α-dependent TFEB regulation only occurred in KCs but not RHMs. Instead, in RHMs, HIF-2α promoted mitochondrial reactive oxygen species production and proinflammatory activation by increasing ANT2 expression and mitochondrial permeability transition. Consequently, myeloid lineage-specific or KC-specific HIF-2α depletion or the inhibition of mTOR-dependent TFEB inhibition using antisense oligonucleotide treatment protected against the development of NASH in mice. Moreover, treatment with an HIF-2α-specific inhibitor reduced inflammatory and fibrogenic gene expression in human liver spheroids cultured under a NASH-like condition. Together, our results suggest that macrophage subtype-specific effects of HIF-2α collectively contribute to the proinflammatory activation of liver macrophages, leading to the development of NASH.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Células de Kupffer , Fígado , Ativação de Macrófagos , Hepatopatia Gordurosa não Alcoólica , Células de Kupffer/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Morte Celular , Lisossomos/metabolismo , Fagocitose , Humanos , Espécies Reativas de Oxigênio/metabolismo , Inflamação/patologia , Inflamação/metabolismo , Camundongos Endogâmicos C57BL , Serina-Treonina Quinases TOR/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Macrófagos/metabolismo , Mitocôndrias/metabolismo
4.
Surg Radiol Anat ; 46(10): 1703-1708, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191991

RESUMO

Variant anatomy in the axillary region is of great clinical significance. It is one of the most frequently accessed regions for radical dissection surgery. During routine dissection of embalmed cadavers, we found a rare case of two accessory muscular slips emerging from the lateral border of latissimus dorsi (LD) and the inferolateral border of pectoralis major (PM), crossing the neurovascular structures in the axilla and merging distally together to the brachial fascia at the upper end of humerus below the bicipital groove. The accessory slip from LD is commonly referred to as the "axillary arch" in literature. We identified the accessory slip from the PM crossing over the axilla as pectoralis quartus. These aberrant slips can cause neurovascular compression in the axilla and can have clinical implications. Prior knowledge of the variant anatomy is the key to successful surgery in the axilla, thereby avoiding inadvertent injuries and post-operative complications.


Assuntos
Variação Anatômica , Axila , Cadáver , Músculos Peitorais , Humanos , Músculos Peitorais/anormalidades , Músculos Peitorais/anatomia & histologia , Axila/anormalidades , Dissecação , Músculos Superficiais do Dorso/transplante , Músculos Superficiais do Dorso/anormalidades , Masculino , Feminino
5.
Surg Radiol Anat ; 46(10): 1749-1752, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39093462

RESUMO

PURPOSE: The saphenous nerve is a predominantly sensory nerve. It is the longest nerve of the body which supplies the skin of the medial side of the leg and foot as far as the ball of the great toe. We present here an unusual motor branch of the saphenous nerve to the sartorius muscle. METHOD: Institutional guidelines for use of human cadaver were followed. Routine dissection of the lower limbs for undergraduate medical teaching was performed in a 67 years old female cadaver employing standard methods. Relevant gross features of the variations were photographed. H&E staining of relevant structure was done and photomicrographed. RESULTS: The unusual motor branch to Sartorius was observed in the right thigh. The branch was given off in the lower third of the thigh after the saphenous nerve exited the adductor canal. The branch was distinctly seen entering the substance of the sartorius. The structure was confirmed to be a peripheral nerve by histological examination. The saphenous nerve then descended between the sartorius and gracilis tendons, pierced the fascia lata and became cutaneous. CONCLUSION: The motor branch to the sartorius muscle is a very rare branch whose knowledge is important for clinicians as it can get damaged during arthroscopy and other knee surgery or during adductor canal block.


Assuntos
Variação Anatômica , Cadáver , Músculo Esquelético , Humanos , Feminino , Idoso , Músculo Esquelético/inervação , Músculo Esquelético/anatomia & histologia , Dissecação , Coxa da Perna/inervação , Nervo Femoral/anatomia & histologia
6.
Gut ; 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39117370

RESUMO

BACKGROUND: There are limited prospective data among overweight and obese individuals on the prevalence of advanced fibrosis, and cirrhosis using advanced MRI-based methods in the USA. The aim of this study was to fill that gap in knowledge by prospectively determining the MRI-based prevalence of steatotic liver disease (SLD) and its subcategories, advanced fibrosis and cirrhosis among overweight and obese individuals residing in the USA. METHODS: This is a cross-sectional analysis of prospectively enrolled overweight or obese adults aged 40-75 years from primary care and community-based settings in Southern California. Participants were classified as having SLD if MRI proton density fat fraction ≥5%, and subclassified as metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-associated liver disease (MetALD) and alcohol-related liver disease (ALD) consistently with the new nomenclature guidance per AASLD-EASL-ALEH. Advanced fibrosis and cirrhosis were defined as magnetic resonance elastography (MRE) ≥3.63 kPa and MRE ≥4.67 kPa, respectively. RESULTS: The cohort included 539 participants with mean (±SD) age of 51.5 (±13.1) years and body mass index of 32.6 (±6.2) kg/m2, respectively. The prevalence of SLD, advanced fibrosis and cirrhosis was 75%, 10.8% and 4.5%, respectively. The prevalence of MASLD, MetALD and ALD was 67.3%, 4.8% and 2.6%, respectively. There was no difference in prevalence of advanced fibrosis and cirrhosis among subcategories. CONCLUSIONS: Using advanced MRI methods among community-dwelling overweight and obese adults, the prevalence of cirrhosis was 4.5%. Most common SLD subcategory was MASLD with 67% of individuals, whereas MetALD and ALD were less common. Systematic screening for advanced fibrosis among overweight/obese adults may be considered.

7.
Front Cell Dev Biol ; 12: 1408844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040042

RESUMO

Obesity is a multifaceted metabolic disorder characterized by excessive accumulation of adipose tissue. It is a well-established risk factor for the development and progression of breast cancer. Adipose tissue, which was once regarded solely as a passive energy storage depot, is now acknowledged as an active endocrine organ producing a plethora of bioactive molecules known as adipokines that contribute to the elevation of proinflammatory cytokines and estrogen production due to enhanced aromatase activity. In the context of breast cancer, the crosstalk between adipocytes and cancer cells within the adipose microenvironment exerts profound effects on tumor initiation, progression, and therapeutic resistance. Moreover, adipocytes can engage in direct interactions with breast cancer cells through physical contact and paracrine signaling, thereby facilitating cancer cell survival and invasion. This review endeavors to summarize the current understanding of the intricate interplay between adipocyte-associated factors and breast cancer progression. Furthermore, by discussing the different aspects of breast cancer that can be adversely affected by obesity, this review aims to shed light on potential avenues for new and novel therapeutic interventions.

8.
JAMA Netw Open ; 7(7): e2421846, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39073818

RESUMO

Importance: Epidemiologic data suggest an association of obesity with breast cancer (BC); however, obesity's contribution to early onset and risk of diagnosis with specific molecular subtypes by race is uncertain. Objective: To examine the race-specific association of body mass index with early onset and diagnosis of specific molecular subtypes. Design, Setting, and Participants: This retrospective cohort study included patients with BC diagnosed between October 1, 2017, and March 31, 2022, at 3 University of South Alabama Mitchell Cancer Institute clinics. Participants were also prospectively enrolled for serum leptin measurement. Main Outcomes and Measures: The primary outcome was age at BC onset and specific subtype diagnosis. The secondary outcome was race-specific differences. Odds ratios (ORs) for associations of body mass index with age at onset and subtype were estimated using the Fisher exact test. Race was self-reported. Results: Of the 1085 study patients, 332 (30.6%) were Black with a median age of 58 (IQR, 50-66) years, and 753 (69.4%) were White with a median age of 63 (IQR, 53-71) years. A total of 499 patients (46.0%) had obesity, with Black women with obesity receiving more frequent BC diagnosis than their White counterparts (OR, 2.40; 95% CI, 1.87-3.15; P < .001). In addition, Black women had a significantly higher incidence of early-onset disease (OR, 1.95; 95% CI, 1.33-2.86; P = .001) than White women, and obesity increased this risk significantly in Black women (OR, 2.92; 95% CI, 1.35-6.22; P = .006). Black women with obesity also had a significantly higher risk of luminal A BC (OR, 2.53; 95% CI, 1.81-3.56; P < .001) and triple-negative BC (TNBC) (OR, 2.48; 95% CI, 1.43-4.22; P = .002) diagnosis than White counterparts. Black women, with or without BC, had significantly higher serum leptin levels (median [IQR], 55.3 [40.3-66.2] ng/mL and 29.1 [21.1-46.5] ng/mL, respectively, P < .001) than White women (median [IQR], 33.4 [18.9-47.7] ng/mL and 16.5 [10.0-22.9] ng/mL, respectively), which was associated with higher odds of luminal A disease (OR, 5.25; 95% CI, 1.69-14.32, P = .003). Higher odds of early-onset disease (OR, 3.50; 95% CI, 0.43-23.15; P = .33 for trend), and TNBC diagnosis (OR, 6.00; 95% CI, 0.83-37.27; P = .14 for trend) were also seen, although these outcomes were not statistically significant. Conclusions and Relevance: In this cohort study of patients with BC, obesity and high serum leptin levels were associated with an enhanced risk of early-onset BC and diagnosis of luminal A and TNBC subtypes in Black women. These findings should help in developing strategies to narrow the existing disparity gaps.


Assuntos
Idade de Início , Neoplasias da Mama , Obesidade , População Branca , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/sangue , Obesidade/epidemiologia , Obesidade/genética , Pessoa de Meia-Idade , População Branca/estatística & dados numéricos , Estudos Retrospectivos , Idoso , Negro ou Afro-Americano/estatística & dados numéricos , Índice de Massa Corporal , Alabama/epidemiologia , Leptina/sangue , Estados Unidos/epidemiologia
9.
Cells ; 13(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891030

RESUMO

NeuroHIV affects approximately 30-60% of people living with HIV-1 (PLWH) and is characterized by varying degrees of cognitive impairments, presenting a multifaceted challenge, the underlying cause of which is chronic, low-level neuroinflammation. Such smoldering neuroinflammation is likely an outcome of lifelong reliance on antiretrovirals coupled with residual virus replication in the brains of PLWH. Despite advancements in antiretroviral therapeutics, our understanding of the molecular mechanism(s) driving inflammatory processes in the brain remains limited. Recent times have seen the emergence of non-coding RNAs (ncRNAs) as critical regulators of gene expression, underlying the neuroinflammatory processes in HIV infection, NeuroHIV, and their associated comorbidities. This review explores the role of various classes of ncRNAs and their regulatory functions implicated in HIV infection, neuropathogenesis, and related conditions. The dysregulated expression of ncRNAs is known to exacerbate the neuroinflammatory responses, thus contributing to neurocognitive impairments in PLWH. This review also discusses the diagnostic and therapeutic potential of ncRNAs in HIV infection and its comorbidities, suggesting their utility as non-invasive biomarkers and targets for modulating neuroinflammatory pathways. Understanding these regulatory roles could pave the way for novel diagnostic strategies and therapeutic interventions in the context of HIV and its comorbidities.


Assuntos
Comorbidade , Infecções por HIV , RNA não Traduzido , Humanos , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Infecções por HIV/genética , Infecções por HIV/virologia , Infecções por HIV/complicações , HIV-1/genética
10.
Bratisl Lek Listy ; 125(7): 450-456, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38943507

RESUMO

OBJECTIVE: This study aimed to assess the perceived need among surgical residents to revisit their anatomical knowledge and evaluate their attitude towards integrating clinical anatomists into surgical residency program curriculum. BACKGROUND: While medical students learn human anatomy during undergraduate years, the practical application of clinically oriented anatomy becomes vital in surgical specialties. However, this aspect has not been adequately addressed in Indian surgical residency programs. METHODS: An 11-item questionnaire, including closed-ended and Likert-scale questions, was administered to 153 surgical residents. Consent was obtained, and responses were collected via Google Forms. RESULTS: Half of the respondents (50%) felt confident in their self-directed anatomy learning, but 87% believed integrating clinical anatomists would enhance their surgical expertise. Additionally, 88% saw value in revisiting cadaveric dissection. Third-year residents showed a significantly higher inclination towards cadaveric dissection. Deficiencies in the curriculum and time constraints were identified as major barriers. CONCLUSION: The study highlights a perceived need among surgical residents to augment their anatomical knowledge, advocating for the integration of clinical anatomists and cadaveric dissection into training. A collaborative approach, emphasizing both horizontal and vertical integration of anatomy, is recommended to enhance surgical education and practice. (Tab. 4, Fig. 1, Ref. 25).


Assuntos
Anatomia , Currículo , Internato e Residência , Humanos , Anatomia/educação , Inquéritos e Questionários , Anatomistas , Índia , Feminino , Masculino , Cirurgiões/educação , Dissecação/educação , Atitude do Pessoal de Saúde , Cirurgia Geral/educação
11.
Asian J Neurosurg ; 19(1): 21-25, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38751390

RESUMO

Background Brain is vulnerable to extreme blood glucose levels that may occur due to multiple factors in neurosurgical patients; perioperative use of dexamethasone is the most common. Thus, frequent monitoring of blood sugar levels is advocated. This study aimed to assess correlation between venous blood sugar measured by lab method and capillary blood sugar by glucometer at various time intervals. Materials and Methods This prospective and observational study was conducted in 20 adult patients of either sex, American Society of Anesthesiologists grade I to III, scheduled to undergo brain tumor resection. The patients who were already on dexamethasone and received intraoperatively 8 mg dexamethasone were enrolled. Standard anesthesia technique and intraoperative monitoring were followed in all patients. Venous sample was withdrawn and blood sugar analyzed in laboratory, while at the same time capillary blood sugar was tested by glucometer. The sampling was done at baseline, 1 hourly after dexamethasone administration till 4 hours and then 8, 12, and 24 hours. The correlation between the two values was assessed. Results During the study, 160 venous and 160 capillary blood sugar levels were analyzed. Though capillary blood sugar levels were slightly higher than venous sugar levels, there was strong correlation between the two (Pearson correlation coefficient) with p -value less than 0.05 except at 24 hours when two values were not correlated. Conclusion Capillary blood sugar levels by glucometer have good correlation with venous sugar levels; therefore, this method may be adopted routinely for frequent blood sugar estimation as it is reliable, easy, and practical.

12.
ACS Omega ; 9(17): 19548-19559, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38708262

RESUMO

Carbon dioxide (CO2) is a detrimental greenhouse gas and is the main contributor to global warming. In addressing this environmental challenge, a promising approach emerges through the utilization of deep eutectic solvents (DESs) as an ecofriendly and sustainable medium for effective CO2 capture. Chemically reactive DESs, which form chemical bonds with the CO2, are superior to nonreactive, physically based DESs for CO2 absorption. However, there are no accurate computational models that provide accurate predictions of the CO2 solubility in chemically reactive DESs. Here, we develop machine learning (ML) models to predict the solubility of CO2 in chemically reactive DESs. As training data, we collected 214 data points for the CO2 solubility in 149 different chemically reactive DESs at different temperatures, pressures, and DES molar ratios from published work. The physics-driven input features for the ML models include σ-profile descriptors that quantify the relative probability of a molecular surface segment having a certain screening charge density and were calculated with the first-principle quantum chemical method COSMO-RS. We show here that, although COSMO-RS does not explicitly calculate chemical reaction profiles, the COSMO-RS-derived σ-profile features can be used to predict bond formation. Of the models trained, an artificial neural network (ANN) provides the most accurate CO2 solubility prediction with an average absolute relative deviation of 2.94% on the testing sets. Overall, this work provides ML models that can predict CO2 solubility precisely and thus accelerate the design and application of chemically reactive DESs.

13.
Nat Commun ; 15(1): 911, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291043

RESUMO

Developing atomically synergistic bifunctional catalysts relies on the creation of colocalized active atoms to facilitate distinct elementary steps in catalytic cycles. Herein, we show that the atomically-synergistic binuclear-site catalyst (ABC) consisting of [Formula: see text]-O-Cr6+ on zeolite SSZ-13 displays unique catalytic properties for iso-stoichiometric co-conversion of ethane and CO2. Ethylene selectivity and utilization of converted CO2 can reach 100 % and 99.0% under 500 °C at ethane conversion of 9.6%, respectively. In-situ/ex-situ spectroscopic studies and DFT calculations reveal atomic synergies between acidic Zn and redox Cr sites. [Formula: see text] ([Formula: see text]) sites facilitate ß-C-H bond cleavage in ethane and the formation of Zn-Hδ- hydride, thereby the enhanced basicity promotes CO2 adsorption/activation and prevents ethane C-C bond scission. The redox Cr site accelerates CO2 dissociation by replenishing lattice oxygen and facilitates H2O formation/desorption. This study presents the advantages of the ABC concept, paving the way for the rational design of novel advanced catalysts.

14.
Int J Biol Macromol ; 258(Pt 2): 129092, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38171444

RESUMO

There is a growing incidence in the presence of emergent pollutants like the pesticides and pharmaceuticals in water bodies. The matter of environmental concern is their synthetic and persistent nature which has resulted in induced toxicity/damaging effect to the vital functioning of the different organs in the aquatic community. Traditional adsorbents have exhibited limitations like low stability and minimum reuse ability. Composites of such adsorbents with polysaccharides have demonstrated distinct features like improved surface area, porosity, adsorptivity; improved reusability and structural integrity; improved mechanical strength, thermal stability when applied for the removal of the emergent pollutants. The biocompatibility and biodegradability of such fabricated composites is established; thereby making the water treatment process cost effective, sustainable and environmentally friendly. The present review has dealt with an in-depth, up-dated literature compilation of traditional as well as polysaccharide based composite adsorbents and addressed their performance evaluation for the removal of pharmaceuticals and pesticides from wastewater. A comparative study has revealed the merits of polysaccharide based composites and discussions have been made with a focus on future research directions in the related area.


Assuntos
Poluentes Ambientais , Praguicidas , Poluentes Químicos da Água , Purificação da Água , Adsorção , Polissacarídeos , Águas Residuárias , Poluentes Químicos da Água/química , Purificação da Água/métodos
15.
Mol Cancer Res ; 22(2): 197-208, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37878010

RESUMO

Pancreatic cancer has the worst prognosis among all cancers, underscoring the need for improved management strategies. Dysregulated mitochondrial function is a common feature in several malignancies, including pancreatic cancer. Although mitochondria have their own genome, most mitochondrial proteins are nuclear-encoded and imported by a multi-subunit translocase of the outer mitochondrial membrane (TOMM). TOMM22 is the central receptor of the TOMM complex and plays a role in complex assembly. Pathobiologic roles of TOMM subunits remain largely unexplored. Here we report that TOMM22 protein/mRNA is overexpressed in pancreatic cancer and inversely correlated with disease outcomes. TOMM22 silencing decreased, while its forced overexpression promoted the growth and malignant potential of the pancreatic cancer cells. Increased import of several mitochondrial proteins, including those associated with mitochondrial respiration, was observed upon TOMM22 overexpression which was associated with increased RCI activity, NAD+/NADH ratio, oxygen consumption rate, membrane potential, and ATP production. Inhibition of RCI activity decreased ATP levels and suppressed pancreatic cancer cell growth and malignant behavior confirming that increased TOMM22 expression mediated the phenotypic changes via its modulation of mitochondrial protein import and functions. Altogether, these results suggest that TOMM22 overexpression plays a significant role in pancreatic cancer pathobiology by altering mitochondrial protein import and functions. IMPLICATIONS: TOMM22 bears potential for early diagnostic/prognostic biomarker development and therapeutic targeting for better management of patients with pancreatic cancer.


Assuntos
Proteínas de Transporte da Membrana Mitocondrial , Neoplasias Pancreáticas , Humanos , Trifosfato de Adenosina/metabolismo , Proteínas de Transporte/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial , Proteínas Mitocondriais/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Transporte Proteico
16.
Cancer Metastasis Rev ; 43(1): 409-421, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37950087

RESUMO

MYB transcription factors are encoded by a large family of highly conserved genes from plants to vertebrates. There are three members of the MYB gene family in human, namely, MYB, MYBL1, and MYBL2 that encode MYB/c-MYB, MYBL1/A-MYB, and MYBL2/B-MYB, respectively. MYB was the first member to be identified as a cellular homolog of the v-myb oncogene carried by the avian myeloblastosis virus (AMV) causing leukemia in chickens. Under the normal scenario, MYB is predominantly expressed in hematopoietic tissues, colonic crypts, and neural stem cells and plays a role in maintaining the undifferentiated state of the cells. Over the years, aberrant expression of MYB genes has been reported in several malignancies and recent years have witnessed tremendous progress in understanding of their roles in processes associated with cancer development. Here, we review various MYB alterations reported in cancer along with the roles of MYB family proteins in tumor cell plasticity, therapy resistance, and other hallmarks of cancer. We also discuss studies that provide mechanistic insights into the oncogenic functions of MYB transcription factors to identify potential therapeutic vulnerabilities.


Assuntos
Neoplasias , Fatores de Transcrição , Animais , Humanos , Plasticidade Celular/genética , Galinhas , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias/genética , Fatores de Transcrição/genética
17.
Ultrason Sonochem ; 102: 106721, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38103370

RESUMO

Most ultrasound-based processes root in empirical approaches. Because nearly all advances have been conducted in aqueous systems, there exists a paucity of information on sonoprocessing in other solvents, particularly ionic liquids (ILs). In this work, we modelled an ultrasonic horn-type sonoreactor and investigated the effects of ultrasound power, sonotrode immersion depth, and solvent's thermodynamic properties on acoustic cavitation in nine imidazolium-based and three pyrrolidinium-based ILs. The model accounts for bubbles, acoustic impedance mismatch at interfaces, and treats the ILs as incompressible, Newtonian, and saturated with argon. Following a statistical analysis of the simulation results, we determined that viscosity and ultrasound input power are the most significant variables affecting the intensity of the acoustic pressure field (P), the volume of cavitation zones (V), and the magnitude of the maximum acoustic streaming surface velocity (u). V and u increase with the increase of ultrasound input power and the decrease in viscosity, whereas the magnitude of negative P decreases as ultrasound power and viscosity increase. Probe immersion depth positively correlates with V, but its impact on P and u is insignificant. 1-alkyl-3-methylimidazolium-based ILs yielded the largest V and the fastest acoustic jets - 0.77 cm3 and 24.4 m s-1 for 1-ethyl-3-methylimidazolium chloride at 60 W. 1-methyl-3-(3-sulfopropyl)-imidazolium-based ILs generated the smallest V and lowest u - 0.17 cm3 and 1.7 m s-1 for 1-methyl-3-(3-sulfopropyl)-imidazolium p-toluene sulfonate at 20 W. Sonochemiluminescence experiments validated the model.

18.
Anat Cell Biol ; 57(1): 147-151, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38115734

RESUMO

Atlanto-occipital assimilation is an osseous embryological anomaly of the craniovertebral junction in which the atlas (C1) is fused to the occiput of skull. Embryologically, this assimilation may happen due to failure of the segmentation and separation of the caudal occipital and the cranial cervical sclerotome. The segmentation clock is maintained by NOTCH and WNT signalling pathways along with Hox genes and retinoic acid. This condition is likely to be a consequence of mutation in above mentioned genes. The knowledge of this assimilation may be crucial for the clinicians as it may lead to various neurovascular symptoms. The present case report involves the analysis of atlanto-occipital assimilation with its clinical significance and embryological basis.

19.
iScience ; 26(12): 108487, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38089573

RESUMO

MYB acts as a potentiator of aggressiveness and castration resistance in prostate cancer (PCa) through aberrant activation of androgen receptor (AR) signaling. Since Black men experience higher PCa incidence and mortality than White men, we examined if MYB was differentially expressed in prostate tumors from patients of these racial backgrounds. The data reveal that aberrant MYB expression starts early in precancerous high-grade prostate intraepithelial neoplastic lesions and increases progressively in malignant cells. PCa tissues from Black patients exhibit higher MYB expression than White patients in overall and grade-wise comparisons. MYB also exhibits a positive correlation with AR expression and both display higher expression in advanced tumor stages. Notably, we find that MYB is a better predictor of biochemical recurrence than AR, pre-treatment PSA, or Gleason's grades. These findings establish MYB as a promising molecular target in PCa that could be used for improved risk prediction and therapeutic planning.

20.
FASEB Bioadv ; 5(10): 412-426, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37810173

RESUMO

Early detection and recurrence prediction are challenging in triple-negative breast cancer (TNBC) patients. We aimed to develop mitochondrial DNA (mtDNA)-based liquid biomarkers to improve TNBC management. Mitochondrial genome (MG) enrichment and next-generation sequencing mapped the entire MG in 73 samples (64 tissues and 9 extracellular vesicles [EV] samples) from 32 metastatic TNBCs. We measured mtDNA and cardiolipin (CL) contents, NDUFB8, and SDHB protein expression in tumors and in corresponding circulating EVs. We identified 168 nonsynonymous mtDNA mutations, with 73% (123/186) coding and 27% (45/168) noncoding in nature. Twenty percent of mutations were nucleotide transversions. Respiratory complex I (RCI) was the key target, which harbored 44% (74/168) of the overall mtDNA mutations. A panel of 11 hotspot mtDNA mutations was identified among 19%-38% TNBCs, which were detectable in the serum-derived EVs with 82% specificity. Overall, 38% of the metastatic tumor-signature mtDNA mutations were traceable in the EVs. An appreciable number of mtDNA mutations were homoplasmic (18%, 31/168), novel (14%, 23/168), and potentially pathogenic (9%, 15/168). The overall and RCI-specific mtDNA mutational load was higher in women with African compared to European ancestry accompanied by an exclusive abundance of respiratory complex (RC) protein NDUFB8 (RCI) and SDHB (RCII) therein. Increased mtDNA (p < 0.0001) content was recorded in both tumors and EVs along with an abundance of CL (p = 0.0001) content in the EVs. Aggressive tumor-signature mtDNA mutation detection and measurement of mtDNA and CL contents in the EVs bear the potential to formulate noninvasive early detection and recurrence prediction strategies.

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