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1.
Phys Chem Chem Phys ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655721

RESUMO

We propose a thermodynamic model that combines the Young-Laplace equation and perturbed chain-statistical associating fluid theory (PC-SAFT) equation of state to estimate capillary condensation pressure in microporous and mesoporous sorbents. We adjust the PC-SAFT dispersion-energy parameter when the pore size becomes comparable to the molecular dimension. This modelling framework is applied to diverse systems containing associating and non-associating gases, various sorbents, and a wide range of temperatures. Our simulation results show that under extreme confinement, a higher value of the dispersion-energy parameter (ε) is required. Furthermore, using the experimental saturation pressure data for 18 different associating and non-associating confined fluids, we find that the shift in the PC-SAFT dispersion energy correlates with the ratio of the sorbent mean pore size to the PC-SAFT segment size (rp/σ). By fitting to the capillary condensation data, the relative deviation between the confined and bulk PC-SAFT dispersion energy parameter is only 0.1% at rp/σ = 15; however, this deviation starts to increase exponentially as rp/σ decreases. For a sorbent with large pores, when rp/σ > 15, the capillary condensation pressure results from our model are similar to the predictions from the Kelvin equation. Using a dataset containing 235 saturation pressure data points composed of 18 pure gases and 4 binary mixtures, the overall AARD% from our model is 12.26%, which verifies the good accuracy of our model. Because the mean sorbent pore radius (rp), the PC-SAFT energy parameter (ε), and segment size (σ) are known a priori, our model estimates the corrected energy parameter for small pores and, thus, extends its applicability.

2.
Cancer Rep (Hoboken) ; 7(3): e2029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38517409

RESUMO

BACKGROUND: Cholangiocarcinoma (CCA), as a rare malignancy of the biliary tree, has a poor prognosis most of the time. CCA is highly epigenetically regulated and several long non-coding RNAs (lncRNA) have been investigated to have a diagnostic and prognostic role in CCA. The current study aimed to assess the studies finding relevant lncRNAs in CCA systematically. METHODS: International databases, including PubMed, Cochrane Library, and Embase, were comprehensively searched in order to identify studies investigating any lncRNA in CCA. After screening by title/abstract and full-text, necessary data were extracted. Random-effect meta-analysis was performed for pooling the areas under the curve (AUCs), specificity, and sensitivity of lncRNAs for the diagnosis of CCA. RESULTS: A total of 33 studies were chosen to be included in the final analysis, comprised of 2677 patients. Meta-analysis of AUCs for evaluation of CCA resulted in pooled AUC of 0.79 (95% CI: 0.75-0.82; I2 = 69.11, p < .01). Additionally, overall sensitivity of 0.80 (95% CI 0.75-0.84) and specificity of 0.77 (95% CI: 0.68-0.84) were observed. Measurement of lncRANs in the assessment of CCA also improved overall survival significantly (effect size 1.61, 95% CI: 1.39-1.82). A similar result was found for progression-free survival (effect size 1.57, 95% CI: 1.20-1.93). CONCLUSION: Based on our findings, lncRNAs showed promising results as biomarkers in the diagnosis of CCA since they had acceptable sensitivity and specificity, in addition to the fact that improved survival in this poor prognosis cancer. Further studies might be needed to address this issue and find the best clinically useful lncRNA.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Sensibilidade e Especificidade , Ductos Biliares Intra-Hepáticos/patologia
3.
Clin. transl. oncol. (Print) ; 26(3): 574-583, mar. 2024.
Artigo em Inglês | IBECS | ID: ibc-230788

RESUMO

Renal cell carcinoma accounts for two to three percent of adult malignancies and can lead to inferior vena cava (IVC) thrombosis. This condition can decrease the rate of 5-year survival for patients to 60%. The treatment of choice in such cases is radical nephrectomy and inferior vena cava thrombectomy. This surgery is one of the most challenging due to many perioperative complications. There are many controversial methods reported in the literature. Achieving the free of tumor IVC wall and the possibility of thrombectomy in cases of level III and level IV IVC thrombosis are two essential matters previously advocated open approaches. Nevertheless, open approaches are being replaced by minimally invasive techniques despite the difficulty of the surgical management of IVC thrombectomy. This paper aims to review recent evidence about new surgical methods and a comparison of open, laparoscopic, and robotic approaches. In this review, we present the latest surgical strategies for IVC thrombectomy and compare open and minimally invasive approaches to achieve the optimal surgical technique. Due to the different anatomy of the left and right kidneys and variable extension of venous thrombosis, we investigate surgical methods for left and right kidney cancer and each level of IVC venous thrombosis separately (AU)


Assuntos
Humanos , Adulto , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Nefrectomia , Estudos Retrospectivos , Trombectomia/efeitos adversos , Trombectomia/métodos , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia
4.
Rev Neurosci ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38452377

RESUMO

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with a poor prognosis leading to death. The diagnosis and treatment of ALS are inherently challenging due to its complex pathomechanism. Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides involved in different cellular processes, incisively gene expression. In recent years, more studies have been conducted on lncRNA classes and interference in different disease pathologies, showing their promising contribution to diagnosing and treating neurodegenerative diseases. In this review, we discussed the role of lncRNAs like NEAT1 and C9orf72-as in ALS pathogenesis mechanisms caused by mutations in different genes, including TAR DNA-binding protein-43 (TDP-43), fused in sarcoma (FUS), superoxide dismutase type 1 (SOD1). NEAT1 is a well-established lncRNA in ALS pathogenesis; hence, we elaborate on its involvement in forming paraspeckles, stress response, inflammatory response, and apoptosis. Furthermore, antisense lncRNAs (as-lncRNAs), a key group of transcripts from the opposite strand of genes, including ZEB1-AS1 and ATXN2-AS, are discussed as newly identified components in the pathology of ALS. Ultimately, we review the current standing of using lncRNAs as biomarkers and therapeutic agents and the future vision of further studies on lncRNA applications.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38488239

RESUMO

OBJECTIVE: Provide clinicians with current evidence for biologic therapy in children with chronic rhinosinusitis with nasal polyposis (CRSwNP). DATA SOURCES: PubMed, MEDLINE, Cochrane, and clinical trial registries. REVIEW METHODS: Key search terms related to biologic therapy in pediatric CRSwNP were identified via a structured query of current medical literature and clinical trial databases. CONCLUSIONS: There is a dearth of active clinical trials and research studies for biologics targeting pediatric CRSwNP. There is an ongoing compassionate-use clinical trial involving Dupilumab for children with nasal polyps as well as only 1 published work specifically focused on Dupilumab for pediatric CRSwNP in the setting of aspirin-exacerbated respiratory disease. IMPLICATIONS FOR PRACTICE: For children with atopic dermatitis, asthma, and chronic idiopathic urticaria, biologic therapies such as Omalizumab, Dupilumab, and Mepolizumab have gained Food and Drug Administration approval. The role of biologic therapy in pediatric CRSwNP demonstrates significant promise in the comprehensive management of the unified airway. Additional Phase III trials are necessary to broaden clinical indications for children with comorbid conditions and complex sinonasal disease.

6.
Int J Pharm ; 654: 123923, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38403091

RESUMO

Cancer continues to be a significant worldwide cause of mortality. This underscores the urgent need for novel strategies to complement and overcome the limitations of conventional therapies, such as imprecise targeting and drug resistance. Cancer Immunotherapy utilizes the body's immune system to target malignant cells, reducing harm to healthy tissue. Nevertheless, the efficacy of immunotherapy exhibits variation across individuals and has the potential to induce autoimmune responses. Biomimetic nanoparticles (bNPs) have transformative potential in cancer immunotherapy, promising improved accurate targeting, immune system activation, and resistance mechanisms, while also reducing the occurrence of systemic autoimmune side effects. This integration offers opportunities for personalized medicine and better therapeutic outcomes. Despite considerable potential, bNPs face barriers like insufficient targeting, restricted biological stability, and interactions within the tumor microenvironment. The resolution of these concerns is crucial in order to expedite the integration of bNPs from the research setting into clinical therapeutic uses. In addition, optimizing manufacturing processes and reducing bNP-related costs are essential for practical implementation. The present research introduces comprehensive classifications of bNPs as well as recent achievements in their application in cancer immunotherapies, emphasizing the need to address barriers for swift clinical integration.


Assuntos
Nanopartículas , Neoplasias , Humanos , Biomimética , Nanotecnologia , Neoplasias/tratamento farmacológico , Nanopartículas/uso terapêutico , Imunoterapia , Microambiente Tumoral
7.
Rev Neurosci ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38347675

RESUMO

Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARÉ£, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARÉ£ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.

8.
J Biol Eng ; 18(1): 14, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317174

RESUMO

Bone metastasis is considered as a considerable challenge for breast cancer patients. Various in vitro and in vivo models have been developed to examine this occurrence. In vitro models are employed to simulate the intricate tumor microenvironment, investigate the interplay between cells and their adjacent microenvironment, and evaluate the effectiveness of therapeutic interventions for tumors. The endeavor to replicate the latency period of bone metastasis in animal models has presented a challenge, primarily due to the necessity of primary tumor removal and the presence of multiple potential metastatic sites.The utilization of novel bone metastasis models, including three-dimensional (3D) models, has been proposed as a promising approach to overcome the constraints associated with conventional 2D and animal models. However, existing 3D models are limited by various factors, such as irregular cellular proliferation, autofluorescence, and changes in genetic and epigenetic expression. The imperative for the advancement of future applications of 3D models lies in their standardization and automation. The utilization of artificial intelligence exhibits the capability to predict cellular behavior through the examination of substrate materials' chemical composition, geometry, and mechanical performance. The implementation of these algorithms possesses the capability to predict the progression and proliferation of cancer. This paper reviewed the mechanisms of bone metastasis following primary breast cancer. Current models of breast cancer bone metastasis, along with their challenges, as well as the future perspectives of using these models for translational drug development, were discussed.

9.
Health Sci Rep ; 7(2): e1873, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332930

RESUMO

Background and Aim: In late 2021, the world faced the rapid spread of the SARS-CoV-2 Omicron variant, which quickly became the variant of concern. In April 2022, two new lineages of Omicron (BA.4/BA.5) emerged from Africa, where they caused the fifth wave of infection. Method: We searched PubMed, Google Scholar, and Scopus online databases up to December 2023 for founding relevant studies. Results: BA.4 and BA.5 subgroups, with changes in the spike protein, have a greater ability to escape from the immune system, which was possible with the help of L452R and F486V mutations. Epidemiologically, these evolving subtypes show similarities to seasonal influenza but with higher mortality rates. The symptoms of these subgroups are different from the previous types in the form of upper respiratory symptoms. Antiviral treatments, the use of antibodies such as bebtelovimab, and the development of vaccines are promising. Conclusion: Consequently, we must continue to be vigilant in our joint surveillance efforts against COVID-19 in diagnosis and treatment.

10.
Mult Scler Relat Disord ; 83: 105472, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38316078

RESUMO

BACKGROUND: Upper respiratory viral infections have long been considered triggers for multiple sclerosis (MS) relapse and exacerbation. The possible effects of SARS-CoV-2 infection on MS relapse and deterioration remain controversial. METHODS: We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science databases to find relevant studies assessing changes in relapse rates or Expanded Disability Status Scale (EDSS) following COVID-19 in people with MS. Meta-analyses were performed, and to investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted. RESULTS: We included 14 studies in our systematic review and meta-analysis. The meta-analysis demonstrated that COVID-19 was not associated with a rise in relapse rate (risk ratio (RR): 0.97, 95 % confidence interval (CI): 0.67, 1.41, p-value: 0.87) or a rise in EDSS (standardized mean difference (SMD): -0.09, 95 % CI: -0.22, 0.03, p-value: 0.13). The analysis of EDSS changes indicated a significant heterogeneity (I2: 55 %, p-value: 0.01). Other analyses were not statistically significant. CONCLUSIONS: COVID-19 infection was not associated with an increased risk of relapse and clinical deterioration in people with MS.


Assuntos
COVID-19 , Esclerose Múltipla , Humanos , COVID-19/complicações , SARS-CoV-2 , Esclerose Múltipla/complicações , Esclerose Múltipla/epidemiologia , Doença Crônica , Recidiva
11.
Acta Neurol Belg ; 124(2): 533-542, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38267724

RESUMO

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is critical for enhancing the survival and growth of neurons and modulating the synaptic plasticity. BDNF levels have been demonstrated to be changed in plasma and cerebrospinal fluid (CSF) following brain insults such as inflammation or ischemia or infection in several studies. Currently, there is no systematic review regarding BDNF levels in encephalitis or encephalopathy patients. Considering inconsistency between studies, we aimed to pool the data from existing studies to determine whether blood or CSF levels of BDNF are different in patients with encephalopathy/encephalitis. METHODS: We comprehensively searched Web of Science, PubMed, Scopus, and Embase databases to identify eligible studies. The last search occurred in December 2022. RESULTS: 12 studies met our inclusion criteria and ten studies including 283 patients and 323 healthy controls were enrolled in this meta-analysis. In comparison to controls, patients with encephalitis/encephalopathy had higher levels of BDNF in their CSF [standardized mean difference (SMD) = 1.48, 95% CI 0.18-2.77; P = 0.03)], while their blood levels of BDNF did not differ significantly [standardized mean difference (SMD) = 0.27, 95% CI = - 0.71 to 1.25; P = 0.58)]. Moreover, regarding the heterogeneity among studies reporting BDNF blood levels, we performed two subgroup analyses based on the disease etiology and the specimen (plasma and serum); none of them indicated statistically significant difference in BDNF levels between the subgroups (P = 0.41 and 0.20, respectively). CONCLUSION: Meta-analysis provides evidence that patients with encephalopathy/encephalitis have higher CSF levels of BDNF compared to controls.


Assuntos
Encefalopatias , Encefalite , Humanos , Fator Neurotrófico Derivado do Encéfalo/líquido cefalorraquidiano , Biomarcadores , Encéfalo
12.
Clin Immunol ; 259: 109896, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38184287

RESUMO

BACKGROUND: Inborn errors of immunity (IEI) are a diverse range of genetic immune system illnesses affecting the innate and/or adaptive immune systems. Variable expressivity and incomplete penetrance have been reported in IEI patients with similar clinical diagnoses or even the same genetic mutation. METHODS: Among all recorded patients in the national IEI registry, 193 families with multiple cases have been recognized. Clinical, laboratory and genetic variability were compared between 451 patients with different IEI entities. RESULTS: The diagnosis of the first children led to the earlier diagnosis, lower diagnostic delay, timely treatment and improved survival in the second children in the majority of IEI. The highest discordance in familial lymphoproliferation, autoimmunity and malignancy were respectively observed in STK4 deficiency, DNMT3B deficiency and ATM deficiency. Regarding immunological heterogeneity within a unique family with multiple cases of IEI, the highest discordance in CD3+, CD4+, CD19+, IgM and IgA levels was observed in syndromic combined immunodeficiencies (CID), while non-syndromic CID particularly severe combined immunodeficiency (SCID) manifested the highest discordance in IgG levels. Identification of the first ATM-deficient patient can lead to improved care and better survival in the next IEI children from the same family. CONCLUSION: Intrafamilial heterogeneity in immunological and/or clinical features could be observed in families with multiple cases of IEI indicating the indisputable role of appropriate treatment and preventive environmental factors besides specific gene mutations in the variable observed penetrance or expressivity of the disease. This also emphasizes the importance of implementing genetic evaluation in all members of a family with a history of IEI even if there is no suspicion of an underlying IEI as other factors besides the underlying genetic defects might cause a milder phenotype or delay in presentation of clinical features. Thus, affected patients could be timely diagnosed and treated, and their quality of life and survival would improve.


Assuntos
Diagnóstico Tardio , Qualidade de Vida , Criança , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Antígenos CD19 , Autoimunidade , Proteínas Serina-Treonina Quinases , Peptídeos e Proteínas de Sinalização Intracelular
13.
Stem Cell Rev Rep ; 20(3): 637-655, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38270744

RESUMO

Cleft lip and/or palate (CLP) is a prevalent congenital craniofacial abnormality that can lead to difficulties in eating, speaking, hearing, and psychological distress. The traditional approach for treating CLP involves bone graft surgery, which has limitations, post-surgical complications, and donor site morbidity. However, regenerative medicine has emerged as a promising alternative, employing a combination of stem cells, growth factors, and scaffolds to promote tissue regeneration. This review aims to provide a comprehensive overview of stem cell-based regenerative approaches in the management of CLP. A thorough search was conducted in the Medline/PubMed and Scopus databases, including cohort studies, randomized controlled trials, case series, case controls, case reports, and animal studies. The identified studies were categorized into two main groups: clinical studies involving human subjects and in vivo studies using animal models. While there are only a limited number of studies investigating the combined use of stem cells and scaffolds for CLP treatment, they have shown promising results. Various types of stem cells have been utilized in conjunction with scaffolds. Importantly, regenerative methods have been successfully applied to patients across a broad range of age groups. The collective findings derived from the reviewed studies consistently support the notion that regenerative medicine holds potential advantages over conventional bone grafting and represents a promising therapeutic option for CLP. However, future well-designed clinical trials, encompassing diverse combinations of stem cells and scaffolds, are warranted to establish the clinical efficacy of these interventions with a larger number of patients.


Assuntos
Fenda Labial , Fissura Palatina , Humanos , Fenda Labial/cirurgia , Fenda Labial/complicações , Fissura Palatina/cirurgia , Fissura Palatina/complicações , Medicina Regenerativa , Células-Tronco
14.
Med Res Rev ; 44(3): 1267-1325, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38226452

RESUMO

Neuropsychiatric disorders denote a broad range of illnesses involving neurology and psychiatry. These disorders include depressive disorders, anxiety, schizophrenia, bipolar disorder, attention deficit hyperactivity disorder, autism spectrum disorders, headaches, and epilepsy. In addition to their main neuropathology that lies in the central nervous system (CNS), lately, studies have highlighted the role of immunity and neuroinflammation in neuropsychiatric disorders. Toll-like receptors (TLRs) are innate receptors that act as a bridge between the innate and adaptive immune systems via adaptor proteins (e.g., MYD88) and downstream elements; TLRs are classified into 13 families that are involved in normal function and illnesses of the CNS. TLRs expression affects the course of neuropsychiatric disorders, and is influenced during their pharmacotherapy; For example, the expression of multiple TLRs is normalized during the major depressive disorder pharmacotherapy. Here, the role of TLRs in neuroimmunology, treatment, and management of neuropsychiatric disorders is discussed. We recommend longitudinal studies to comparatively assess the cell-type-specific expression of TLRs during treatment, illness progression, and remission. Also, further research should explore molecular insights into TLRs regulation and related pathways.


Assuntos
Transtorno Depressivo Maior , Humanos , Receptores Toll-Like/metabolismo , Sistema Nervoso Central , Imunidade Inata
15.
Eur J Med Res ; 29(1): 55, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38229141

RESUMO

BACKGROUND: Patients with autoimmune and immune-mediated diseases (AI-IMD) are at greater risk of COVID-19 infection; therefore, they should be prioritized in vaccination programs. However, there are concerns regarding the safety of COVID-19 vaccines in terms of disease relapse, flare, or exacerbation. In this study, we aimed to provide a more precise and reliable vision using systematic review and meta-analysis. METHODS: PubMed-MEDLINE, Embase, and Web of Science were searched for original articles reporting the relapse/flare in adult patients with AI-IMD between June 1, 2020 and September 25, 2022. Subgroup analysis and sensitivity analysis were conducted to investigate the sources of heterogeneity. Statistical analysis was performed using R software. RESULTS: A total of 134 observations of various AI-IMDs across 74 studies assessed the rate of relapse, flare, or exacerbation in AI-IMD patients. Accordingly, the crude overall prevalence of relapse, flare, or exacerbation was 6.28% (95% CI [4.78%; 7.95%], I2 = 97.6%), changing from 6.28% (I2 = 97.6%) to 6.24% (I2 = 65.1%) after removing the outliers. AI-IMD patients administering mRNA, vector-based, and inactive vaccines showed 8.13% ([5.6%; 11.03%], I2 = 98.1%), 0.32% ([0.0%; 4.03%], I2 = 93.5%), and 3.07% ([1.09%; 5.9%], I2 = 96.2%) relapse, flare, or exacerbation, respectively (p-value = 0.0086). In terms of disease category, nephrologic (26.66%) and hematologic (14.12%) disorders had the highest and dermatologic (4.81%) and neurologic (2.62%) disorders exhibited to have the lowest crude prevalence of relapse, flare, or exacerbation (p-value < 0.0001). CONCLUSION: The risk of flare/relapse/exacerbation in AI-IMD patients is found to be minimal, especially with vector-based vaccines. Vaccination against COVID-19 is recommended in this population.


Assuntos
Doenças Autoimunes , COVID-19 , Adulto , Humanos , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinação , Doença Crônica
16.
Proc Natl Acad Sci U S A ; 121(3): e2315354120, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38194459

RESUMO

The emergence of Omicron lineages and descendent subvariants continues to present a severe threat to the effectiveness of vaccines and therapeutic antibodies. We have previously suggested that an insufficient mucosal immunoglobulin A (IgA) response induced by the mRNA vaccines is associated with a surge in breakthrough infections. Here, we further show that the intramuscular mRNA and/or inactivated vaccines cannot sufficiently boost the mucosal secretory IgA response in uninfected individuals, particularly against the Omicron variant. We thus engineered and characterized recombinant monomeric, dimeric, and secretory IgA1 antibodies derived from four neutralizing IgG monoclonal antibodies (mAbs 01A05, rmAb23, DXP-604, and XG014) targeting the receptor-binding domain of the spike protein. Compared to their parental IgG antibodies, dimeric and secretory IgA1 antibodies showed a higher neutralizing activity against different variants of concern (VOCs), in part due to an increased avidity. Importantly, the dimeric or secretory IgA1 form of the DXP-604 antibody significantly outperformed its parental IgG antibody, and neutralized the Omicron lineages BA.1, BA.2, and BA.4/5 with a 25- to 75-fold increase in potency. In human angiotensin converting enzyme 2 (ACE2) transgenic mice, a single intranasal dose of the dimeric IgA DXP-604 conferred prophylactic and therapeutic protection against Omicron BA.5. Thus, dimeric or secretory IgA delivered by nasal administration may potentially be exploited for the treatment and prevention of Omicron infection, thereby providing an alternative tool for combating immune evasion by the current circulating subvariants and, potentially, future VOCs.


Assuntos
Anticorpos Monoclonais , Imunoglobulina A Secretora , Animais , Camundongos , Humanos , Imunoglobulina G , Imunoglobulina A , Administração Intranasal , Camundongos Transgênicos
17.
J Cell Mol Med ; 28(3): e18109, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38193829

RESUMO

Recently, long noncoding RNAs (lncRNAs) have been applied as biomarkers for melanoma patients. In this systematic review and meta-analysis, we investigated the diagnostic and prognostic value of lncRNAs. We used the keywords 'lncRNA' and 'melanoma' to search databases for studies published before June 14th, 2023. The specificity, sensitivity and AUC were utilized to assess diagnostic accuracy and the prognostic value was assessed using overall survival, progression-free survival and disease-free survival hazard ratios. After screening 1191 articles, we included seven studies in the diagnostic evaluation section and 17 studies in the prognosis evaluation section. The Reitsma bivariate model estimated a cumulative sensitivity of 0.724 (95% CI: 0.659-0.781, p < 0.001) and specificity of 0.812 (95% CI: 0.752-0.859, p < 0.001). The pooled AUC was 0.780 (95% CI: 0.749-0.811, p < 0.0001). The HR for overall survival was 2.723 (95% CI: 2.259-3.283, p < 0.0001). Two studies reported an HR for overall survival less than one, with an HR of 0.348 (95% CI: 0.200-0.607, p < 0.0002). The HR for progression-free survival was 2.913 (95% CI: 2.050-4.138, p < 0.0001). Four studies reported an HR less than one, with an HR of 0.457 (95% CI: 0.256-0.817). The HR for disease-free survival was 2.760 (95% CI: 2.009-3.792, p < 0.0001). In conclusion, the expression of lncRNAs in melanoma patients affects survival and prognosis. LncRNAs can also be employed as diagnostic biomarkers.


Assuntos
Melanoma , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Prognóstico , Biomarcadores Tumorais/genética , Modelos de Riscos Proporcionais
18.
Artigo em Inglês | MEDLINE | ID: mdl-38279762

RESUMO

BACKGROUND: Involvement of gastrointestinal inflammation in Parkinson's disease (PD) pathogenesis and movement have progressively emerged. Inflammation is involved in the etiology of both PD and inflammatory bowel disease (IBD). Transformations in leucine-rich recurrent kinase 2 (LRRK2) are among the best hereditary supporters of IBD and PD. Elevated levels of LRRK2 have been reported in stimulated colonic tissue from IBD patients and peripheral invulnerable cells from irregular PD patients; thus, it is thought that LRRK2 directs inflammatory cycles. OBJECTIVE: Since its revelation, LRRK2 has been seriously linked in neurons, albeit various lines of proof affirmed that LRRK2 is profoundly communicated in invulnerable cells. Subsequently, LRRK2 might sit at a junction by which stomach inflammation and higher LRRK2 levels in IBD might be a biomarker of expanded risk for inconsistent PD or potentially may address a manageable helpful objective in incendiary sicknesses that increment the risk of PD. Here, we discuss how PD and IBD share covering aggregates, especially regarding LRRK2 and present inhibitors, which could be a helpful objective in ongoing treatments. METHOD: English data were obtained from Google Scholar, PubMed, Scopus, and Cochrane library studies published between 1990-December 2022. RESULT: Inhibitors of the LRRK2 pathway can be considered as the novel treatment approaches for IBD and PD treatment. CONCLUSION: Common mediators and pathways are involved in the pathophysiology of IBD and PD, which are majorly correlated with inflammatory situations. Such diseases could be used for further clinical investigations.

19.
Eur J Haematol ; 112(2): 153-173, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37254607

RESUMO

Mesenchymal stromal cells (MSCs) and chimeric antigen receptor (CAR)-T cells are two core elements in cell therapy procedures. MSCs have significant immunomodulatory effects that alleviate inflammation in the tissue regeneration process, while administration of specific chemokines and adhesive molecules would primarily facilitate CAR-T cell trafficking into solid tumors. Multiple parameters affect cell homing, including the recipient's age, the number of cell passages, proper cell culture, and the delivery method. In addition, several chemokines are involved in the tumor microenvironment, affecting the homing procedure. This review discusses parameters that improve the efficiency of cell homing and significant cell therapy challenges. Emerging comprehensive mechanistic strategies such as non-systemic and systemic homing that revealed a significant role in cell therapy remodeling were also reviewed. Finally, the primary implications for the development of combination therapies that incorporate both MSCs and CAR-T cells for cancer treatment were discussed.


Assuntos
Células-Tronco Mesenquimais , Neoplasias , Humanos , Medicina Regenerativa/métodos , Neoplasias/terapia , Linfócitos T , Quimiocinas , Microambiente Tumoral , Imunoterapia Adotiva/métodos
20.
Crit Rev Oncol Hematol ; 193: 104225, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38049077

RESUMO

Lymphoma is known as the third most common malignancy in children, and its prevalence and mortality are increasing. Common treatments, including chemotherapy, radiotherapy, and also surgery, despite their efficacy, have many side effects and, have a high chance of disease relapse. Immune Checkpoint Inhibitors (ICIs) offer a promising alternative with potentially fewer risks of relapse and toxicity. This review article aims to investigate the efficacy and safety of ICIs, either as monotherapy or in combination, for pediatric lymphoma patients. ICIs have revolutionized cancer treatment in recent years and have shown remarkable results in several adult cancers. However, their efficacy in treating pediatrics requires further investigation. Nevertheless, some ICIs, including nivolumab, pembrolizumab, and ipilimumab, have demonstrated encouraging outcomes. ICIs therapy is not without risks and can cause side effects, including rash, itching, vitiligo, abdominal pain, diarrhea, dysphagia, epigastric pain, nausea, vomiting, thyroid, and pituitary dysfunction. Overall, this review article highlights the potential benefits and risks of ICIs in treating pediatric lymphoma.


Assuntos
Antineoplásicos Imunológicos , Linfoma , Humanos , Criança , Inibidores de Checkpoint Imunológico , Antineoplásicos Imunológicos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma/tratamento farmacológico , Recidiva
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