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1.
Crit Rev Eukaryot Gene Expr ; 34(3): 83-99, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38305291

RESUMO

In Crohn's disease (CD), gut dysbiosis is marked by the prevalence of pathogenic bacterial species. Although several microbes have been reported as risk factors or causative agents of CD, it is not yet clear which is the real trigger of the disease. Thirty years ago, a new pathovar of Escherichia coli strain was isolated in the ileal mucosa of CD patients. This strain, called adherent invasive E. coli (AIEC), for its ability to invade the intestinal mucosa, could represent the causative agent of the disease. Several authors studied the mechanisms by which the AIEC penetrate and replicate within macrophages, and release inflammatory cytokines sustaining inflammation. In this review we will discuss about the role of AIEC in the pathogenesis of CD, the virulence factors mediating adhesion and invasion of AIEC in mucosal tissue, the environmental conditions improving AIEC survival and replication within macrophages. Finally, we will also give an overview of the new strategies developed to limit AIEC overgrowth.


Assuntos
Doença de Crohn , Infecções por Escherichia coli , Humanos , Doença de Crohn/epidemiologia , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Escherichia coli , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Aderência Bacteriana , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia
2.
Cardiovasc Diabetol ; 22(1): 94, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085892

RESUMO

BACKGROUND: Women have a high risk of frailty independently of age and menopause state. Diabetes and hypertension increase the risk of frailty and cognitive impairment. Metformin has been employed in post-menopausal women and some reports have shown encouraging effects in terms of attenuated frailty. However, the impact on cognitive performance of a recently introduced extended-release formulation of metformin has never been explored. METHODS: We studied consecutive frail hypertensive and diabetic older women presenting at the ASL (local health authority of the Italian Ministry of Health) Avellino, Italy, from June 2021 to August 2022, who were treated or not with extended-release metformin. We included a control group of frail older males with diabetes and hypertension treated with extended-release metformin and a control group of frail older women with diabetes and hypertension treated with regular metformin. RESULTS: A total of 145 patients successfully completed the study. At the end of the 6-month follow-up, we observed a significantly different cognitive performance compared to baseline in the group of frail women treated with extended-release metformin (p: 0.007). Then, we compared the follow-up groups and we observed significant differences between frail women treated vs. untreated (p: 0.041), between treated frail women and treated frail men (p: 0.016), and between women treated with extended-release metformin vs. women treated with regular metformin (p: 0.048). We confirmed the crucial role of extended-release metformin applying a multivariable logistic analysis to adjust for potential confounders. CONCLUSIONS: We evidenced, for the first time to the best of our knowledge, the favorable effects on cognitive impairment of extended-release metformin in frail women with diabetes and hypertension.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Fragilidade , Hipertensão , Masculino , Idoso , Humanos , Feminino , Fragilidade/diagnóstico , Fragilidade/tratamento farmacológico , Idoso Fragilizado/psicologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico
3.
Int J Mol Sci ; 23(22)2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36430727

RESUMO

Tumor diseases are unfortunately quick spreading, even though numerous studies are under way to improve early diagnosis and targeted treatments that take into account both the different characteristics associated with the various tumor types and the conditions of individual patients. In recent years, studies have focused on the role of ion channels in tumor development, as these proteins are involved in several cellular processes relevant to neoplastic transformation. Among all ion channels, many studies have focused on the superfamily of Transient Receptor Potential (TRP) channels, which are non-selective cation channels mediating extracellular Ca2+ influx. In this review, we examined the role of different endothelial TRP channel isoforms in tumor vessel formation, a process that is essential in tumor growth and metastasis.


Assuntos
Neoplasias , Canais de Potencial de Receptor Transitório , Humanos , Canais de Potencial de Receptor Transitório/genética , Canais de Potencial de Receptor Transitório/metabolismo , Isoformas de Proteínas/metabolismo
4.
J Cell Physiol ; 235(6): 5041-5049, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31898324

RESUMO

There are many factors contributing to the development of gastrointestinal diseases, grouped into genetic, environmental, and lifestyle factors. In recent years attention has fallen on pathogens; in particular, Bacteroides fragilis, Fusobacterium nucleatum, Escherichia coli (E. coli) and Helicobacter pylori have been studied. Several points remain to be clarified, and above all, as regards the adherent-invasive E. coli strains of E. coli, one wonders if they are a cause or a consequence of the disease. In this review, we have tried to clarify some points by examining a series of recent publications regarding the involvement of the bacterium in the pathology, even if other studies are necessary.


Assuntos
Doença de Crohn/patologia , Disbiose/patologia , Doenças Inflamatórias Intestinais/patologia , Bacteroides fragilis/genética , Bacteroides fragilis/patogenicidade , Adesão Celular/genética , Doença de Crohn/genética , Doença de Crohn/microbiologia , Disbiose/genética , Disbiose/microbiologia , Escherichia coli/genética , Escherichia coli/patogenicidade , Fusobacterium nucleatum/genética , Fusobacterium nucleatum/patogenicidade , Helicobacter pylori/genética , Helicobacter pylori/patogenicidade , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia
5.
J Cell Physiol ; 233(5): 3901-3917, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-28816358

RESUMO

Endothelial progenitor cells (EPCs) are a sub-population of bone marrow-derived mononuclear cells that are released in circulation to restore damaged endothelium during its physiological turnover or rescue blood perfusion after an ischemic insult. Additionally, they may be mobilized from perivascular niches located within larger arteries' wall in response to hypoxic conditions. For this reason, EPCs have been regarded as an effective tool to promote revascularization and functional recovery of ischemic hearts, but clinical application failed to exploit the full potential of patients-derived cells. Indeed, the frequency and biological activity of EPCs are compromised in aging individuals or in subjects suffering from severe cardiovascular risk factors. Rejuvenating the reparative phenotype of autologous EPCs through a gene transfer approach has, therefore, been put forward as an alternative approach to enhance their therapeutic potential in cardiovascular patients. An increase in intracellular Ca2+ concentration constitutes a pivotal signal for the activation of the so-called endothelial colony forming cells (ECFCs), the only known truly endothelial EPC subset. Studies from our group showed that the Ca2+ toolkit differs between peripheral blood- and umbilical cord blood (UCB)-derived ECFCs. In the present article, we first discuss how VEGF uses repetitive Ca2+ spikes to regulate angiogenesis in ECFCs and outline how VEGF-induced intracellular Ca2+ oscillations differ between the two ECFC subtypes. We then hypothesize about the possibility to rejuvenate the biological activity of autologous ECFCs by transfecting the cell with the Ca2+ -permeable channel Transient Receptor Potential Canonical 3, which selectively drives the Ca2+ response to VEGF in UCB-derived ECFCs.


Assuntos
Cálcio/metabolismo , Células Progenitoras Endoteliais/citologia , Neovascularização Patológica/terapia , Neovascularização Fisiológica/fisiologia , Canais de Cátion TRPC/metabolismo , Animais , Sangue Fetal/citologia , Humanos
6.
J Cell Physiol ; 233(8): 6224-6231, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29336497

RESUMO

After an acute liver damage, tissue regeneration repairs lesions with degradation of deposed fibrotic material, while mechanisms of tissue restoration are persistently activated following several repeated injuries, inducing deposition of extracellular matrix. (ECM). Factors responsible for ECM remodeling have been identified in a pathway involving a family of zinc-dependent enzyme matrix metalloproteinases (MMPs), together with tissue inhibitor of metalloproteinases (TIMPs). Recent experimental models suggested a role of CCR5 receptor in the genesis of liver fibrosis. Drawing from these background we decided to evaluate the effects of the treatment with the CCR5 inhibitor Maraviroc on LX-2, a human hepatic stellate cell line (HSC). Treatment with Maraviroc resulted in a block in S phase of LX-2 cells with increased expression levels of cyclin D1 and p21 while the expression of p53 was reduced. Treatment with Maraviroc was also able to block the accumulation of fibrillar collagens and extracellular matrix proteins (ECM), as demonstrated by the decrease of specific markers as Collagen type I, α-SMA, and TGF-ß1. In addition we observed a down regulation of both metalloproteins (MMP-2, MMP-9), used for the degradation of the extracellular matrix and their inhibitors (TIMP-1, TIMP-2). The identification of a compound that may modulate the dynamic of liver fibrosis could be crucial in all chronic liver diseases. Maraviroc could play an important role because, in addition to its own anti-HIV activity, it could reduce the release of pro-inflammatory citokynes implicated in liver fibrogenesis.


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Maraviroc/farmacologia , Receptores CCR5/metabolismo , Linhagem Celular , Colágeno Tipo I/metabolismo , Matriz Extracelular/metabolismo , Células Estreladas do Fígado/metabolismo , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cirrose Hepática/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Fase S/efeitos dos fármacos , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
7.
Int J Mol Sci ; 19(4)2018 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-29561829

RESUMO

BACKGROUND: Neurovascular coupling (NVC) is the mechanism whereby an increase in neuronal activity (NA) leads to local elevation in cerebral blood flow (CBF) to match the metabolic requirements of firing neurons. Following synaptic activity, an increase in neuronal and/or astrocyte Ca2+ concentration leads to the synthesis of multiple vasoactive messengers. Curiously, the role of endothelial Ca2+ signaling in NVC has been rather neglected, although endothelial cells are known to control the vascular tone in a Ca2+-dependent manner throughout peripheral vasculature. METHODS: We analyzed the literature in search of the most recent updates on the potential role of endothelial Ca2+ signaling in NVC. RESULTS: We found that several neurotransmitters (i.e., glutamate and acetylcholine) and neuromodulators (e.g., ATP) can induce dilation of cerebral vessels by inducing an increase in endothelial Ca2+ concentration. This, in turn, results in nitric oxide or prostaglandin E2 release or activate intermediate and small-conductance Ca2+-activated K⁺ channels, which are responsible for endothelial-dependent hyperpolarization (EDH). In addition, brain endothelial cells express multiple transient receptor potential (TRP) channels (i.e., TRPC3, TRPV3, TRPV4, TRPA1), which induce vasodilation by activating EDH. CONCLUSIONS: It is possible to conclude that endothelial Ca2+ signaling is an emerging pathway in the control of NVC.


Assuntos
Sinalização do Cálcio , Células Endoteliais/metabolismo , Acoplamento Neurovascular , Animais , Modelos Biológicos , Modelos Neurológicos , Vasodilatação
8.
J Cell Physiol ; 232(10): 2860-2868, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27925192

RESUMO

Several lines of evidence suggest that adherent-invasive Escherichia coli (AIEC) strains play an important role in Crohn's disease (CD). The objective of this study was to investigate the pathogenic role of two AIEC strains, LF82 and O83:H1, in CD patients. Organ cultures of colonic biopsies from patients were set up to assess the effects of LF82 and O83:H1 on the expression of CEACAM6, LAMP1, HLA-DR, ICAM1 by immunohistochemistry and of IL-8, IFNʏ, and TNF-α genes by RT-PCR. Moreover, on Caco2 cells, we analyzed the cell cycle, the expression of MGMT and DNMT1 genes, and DNA damage induced by LF82 and O83:H1, by FACS, RT-PCR, and DAPI staining, respectively. Epithelial and lamina propria mononuclear cells (LPMNC) expression of CEACAM6 and LAMP1 were higher in biopsies cultured in the presence of both O83:H1 and LF82 than in biopsies cultured with non-pathogenic E. coli. Both AIEC strains induced increased expression of ICAM-1 on blood vessels and HLA-DR on LPMNC. We observed higher levels of TNF-α, IFN-γ, and IL-8 transcripts in biopsies cultured with both AIEC strains than in those cultured with NP. Both LF82 and O83:H1, block the cell cycle into S phase, inducing DNA damage, and modulate the expression of DNMT1 and MGMT genes. Our data suggest that LF82 and 083:H1 strains of E. coli are able to increase in CD colonic biopsies the expression of all the pro-inflammatory cytokines and all the mucosal immune markers investigated. J. Cell. Physiol. 232: 2860-2868, 2017. © 2016 Wiley Periodicals, Inc.


Assuntos
Aderência Bacteriana , Colo/microbiologia , Doença de Crohn/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/patogenicidade , Mucosa Intestinal/microbiologia , Adulto , Idoso , Células CACO-2 , Colo/imunologia , Colo/metabolismo , Colo/patologia , Doença de Crohn/imunologia , Doença de Crohn/metabolismo , Doença de Crohn/patologia , Citocinas/imunologia , Citocinas/metabolismo , Escherichia coli/imunologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/patologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunidade nas Mucosas , Mediadores da Inflamação/imunologia , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Masculino , Pessoa de Meia-Idade , Técnicas de Cultura de Tecidos , Virulência , Adulto Jovem
9.
J Cell Physiol ; 230(8): 1702-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25639461

RESUMO

Helicobacter pylori infects 50% of mankind. The vast majority of H. pylori infection occurs in the developing countries where up to 80% of the middle-aged adults may be infected. Bacterial infection causes an inflammatory response that proceeds through a series of intermediated stages of precancerous lesions (gastritis, atrophy, intestinal metaplasia, and dysplasia). Among infected individuals, approximately 10% develops severe gastric lesions such as peptic ulcer disease, 1-3% progresses to gastric cancer (GC) with a low 5-year survival rate, and 0.1% develops mucosa-associated lymphoid tissue (MALT). GC is one of the most common cancer and the third leading cause of cancer-related deaths worldwide. In this review, we have summarized the most recent papers about molecular mechanisms of H. pylori pathogenesis. The main important steps of H. pylori infection such as adhesion, entry in epithelial gastric cells, activation of intracellular pathways until epigenetic modifications have been described.


Assuntos
Infecções por Helicobacter/fisiopatologia , Helicobacter pylori/patogenicidade , Animais , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Humanos
10.
J Cell Biochem ; 116(10): 2188-94, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25808410

RESUMO

Recently increasing emphasis is placed on preventive health and management of chronic comorbidities avoiding long-term toxicities of antiretroviral therapy (ART). Drawing from this background we decided to use the Saos-2, osteosarcoma cell line, as a cellular model, to evaluate the effects of some antiretroviral drugs such as abacavir (ABC), tenofovir (TDF), efavirenz (EFV), etravirine (ETR), and darunavir (DRV), on bone differentiation related pathways. According to our observation, treatment with TDF and ABC affects the ability of the cells to produce calcium deposits with a reduced expression of type I collagen gene and p21 mRNA, also increasing the activity of Wnt3a related pathway. On the other hand treatment with EFV and DRV was not related to any significant reduction of calcium deposits but displayed a decrease in the expression of Wnt3a at day 14 and Type I Collagen at day 7 compared with untreated cells, even if this last down regulation was not confirmed at day 14. Instead ETR administration to Saos-2 cells increases the calcium deposits collagen type I production, as a result of Wnt3a mRNA overexpression, and of an upregulation of collagen type I expression, being also the only drug able to increase the expression of p21 cdk inhibitor as further marker of terminal differentiation. In summary these data suggest the potential negative interference of TDF and ABC on bone differentiation. DRV and EFV partially affect collagen type I production, instead ETR facilitates a positive bone balance as a result of an increased osteoblasts terminal differentiation.


Assuntos
Desenvolvimento Ósseo/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Alcinos , Terapia Antirretroviral de Alta Atividade , Benzoxazinas/administração & dosagem , Cálcio/metabolismo , Linhagem Celular Tumoral , Colágeno Tipo I/biossíntese , Colágeno Tipo I/genética , Ciclopropanos , Darunavir/administração & dosagem , Didesoxinucleosídeos/administração & dosagem , HIV-1/patogenicidade , Humanos , Nitrilas , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Osteossarcoma/patologia , Piridazinas/administração & dosagem , Pirimidinas , RNA Mensageiro/biossíntese , Tenofovir/administração & dosagem , Proteína Wnt3A/biossíntese , Proteína Wnt3A/genética , Quinases Ativadas por p21/biossíntese , Quinases Ativadas por p21/genética
11.
Tissue Cell ; 88: 102402, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38759523

RESUMO

GATA3 plays critical roles in the development and function of various tissues and organs throughout the body. Likewise, TGF-ß signaling is critical for placental development and can interact with GATA3. We aimed to investigate the involvement of the multifunctional cytokine and transcription factor in trophoblast development. By using immunohistochemistry, we evaluated the localization and expression level of GATA3 and TGF-ß in placentas at term of normal pregnancy and with pre-eclampsia. Up-regulation of both GATA3 and TGF-ß was observed in pathological placentas, with localization in the villus epithelium (syncytiotrophoblast) stroma and decidua. Our data show altered expression of TGF-ß and GATA3, which downstream could lead to a cascade of events that negatively influence trophoblast development and contribute to the pathogenesis of pre-eclampsia.


Assuntos
Fator de Transcrição GATA3 , Placenta , Pré-Eclâmpsia , Fator de Crescimento Transformador beta , Pré-Eclâmpsia/metabolismo , Pré-Eclâmpsia/patologia , Humanos , Gravidez , Feminino , Fator de Transcrição GATA3/metabolismo , Placenta/metabolismo , Placenta/patologia , Fator de Crescimento Transformador beta/metabolismo , Adulto , Trofoblastos/metabolismo , Trofoblastos/patologia
12.
G Ital Nefrol ; 41(2)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38695227

RESUMO

Standard ultrasound (US) finds wide use in renal diseases as a screening procedure, but it is not always able to characterize lesions, especially in differential diagnosis between benign and malignant lesions. In contrast, contrast-enhanced ultrasonography (CEUS) is appropriate in differentiating between solid and cystic lesions as well as between tumors and pseudotumors. We show the case of a nephropathic patient who showed a complex, large, growing renal mass, characterized through a CEUS. This seventy-five-year-old diabetic heart patient showed a 6 cm-complex and plurisected cyst on ultrasound of left kidney. Laboratory data showed the presence of stage IIIb chronic renal failure with GFR 30 ml/min, creatinine 2.33 mg/dl, azotemia 88 mg/dl. The patient performed abdominal CT without contrast medium, showing at the level of the left upper pole, a roundish formation with the dimensions of approximately 70x53x50 mm. At the semiannual checkup, the nephrology examination showed a slight rise in creatinine and, therefore, after six months, it was decided to perform a CT scan without contrast medium again. CT showed a slight increase in the size of the mass located at the left kidney (74x56x57 mm). Given the increased size of the left mass, albeit modest, a CEUS was performed to reach a diriment diagnosis. CEUS concluded for complex cystic formation with presence of intraluminal solid-corpuscular material, with thrombotic-hemorrhagic etiology, in progressive phase of organization, classifiable as Bosniak type II cyst. CEUS in the kidneys is a cost-effective and valuable imaging technique; it is accurate in the characterization of indeterminate lesions and complex cysts.


Assuntos
Meios de Contraste , Ultrassonografia , Humanos , Masculino , Idoso , Nefropatias/diagnóstico por imagem , Doenças Renais Císticas/diagnóstico por imagem
13.
Antibiotics (Basel) ; 13(2)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38391539

RESUMO

Crohn's disease (CD) is a multifactorial chronic disorder that involves a combination of factors, including genetics, immune response, and gut microbiota. Therapy includes salicylates, immunosuppressive agents, corticosteroids, and biologic drugs. International guidelines do not recommend the use of antibiotics for CD patients, except in the case of septic complications. Increasing evidence of the involvement of gut bacteria in this chronic disease supports the rationale for using antibiotics as the primary treatment for active CD. In recent decades, several pathogens have been reported to be involved in the development of CD, but only Escherichia coli (E. coli) and Mycobacterium avium paratubercolosis (MAP) have aroused interest due to their strong association with CD pathogenesis. Several meta-analyses have been published concerning antibiotic treatment for CD patients, but randomized trials testing antibiotic treatment against E. coli and MAP have not shown prolonged benefits and have generated conflicting results; several questions are still unresolved regarding trial design, antibiotic dosing, the formulation used, the treatment course, and the outcome measures. In this paper, we provide an overview and update of the trials testing antibiotic treatment for active CD patients, taking into account the role of pathogens, the mechanisms by which different antibiotics act on harmful pathogens, and antibiotic resistance. Finally, we also present new lines of study for the future regarding the use of antibiotics to treat patients with active CD.

14.
J Pers Med ; 13(7)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37511750

RESUMO

BACKGROUND: Foot drop (FD) is characterized by an inability to lift the foot against gravity because of dorsiflexor muscle weakness. The aim of the present study is to report a clinical case of acute non-traumatic FD in patients with peroneal intraneural ganglion, after performing a scoping review on the methodological management of this disease. METHODS: We performed a review of the literature and reported the case of a 49-year-old man with acute FD caused by an intraneural ganglion cyst of the peroneal nerve. RESULTS: Out of a total of 201 articles, 3 were suitable for our review beyond our case report. The acute FD caused by peroneal intraneural ganglion can be managed by a careful clinical-instrumental differential diagnosis. A targeted surgery with subsequent rehabilitation produced a satisfactory motor recovery. CONCLUSIONS: Acute FD requires an appropriate diagnostic-therapeutic framework to identify and effectively treat the causes in order to promote complete recovery.

15.
J Diet Suppl ; 20(2): 372-389, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36729019

RESUMO

Nutraceuticals have for several years aroused the interest of researchers for their countless properties, including the management of viral infections. In the context of the COVID-19 pandemic, studies and research on the antiviral properties of nutraceuticals have greatly increased. More specifically, over the past two years, researchers have focused on analyzing the possible role of nutraceuticals in reducing the risk of SARS-CoV-2 infection or mitigating the symptoms of COVID-19. Among nutraceuticals, turmeric, extracted from the rhizome of the Curcuma Longa plant, and spirulina, commercial name of the cyanobacterium Arthrospira platensis, have assumed considerable importance in recent years. The purpose of this review is to collect, through a search of the most recent articles on Pubmed, the scientific evidence on the role of these two compounds in the fight against COVID-19. In the last two years many hypotheses, some confirmed by clinical and experimental studies, have been made on the possible use of turmeric against COVID-19, while on spirulina and its possible role against SARS-CoV-2 infection information is much less. The demonstrated antiviral properties of spirulina and the fact that these cyanobacteria may modulate or modify some mechanisms also involved in the onset of COVID-19, lead us to think that it may have the same importance as curcumin in fighting this disease and to speculate on the possible combined use of these two substances to obtain a synergistic effect.


Assuntos
COVID-19 , Curcumina , Spirulina , Humanos , Curcumina/farmacologia , Curcumina/uso terapêutico , SARS-CoV-2 , Pandemias , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico
16.
Tissue Cell ; 82: 102074, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36948081

RESUMO

INTRODUCTION: Recent investigations suggest the potential negative impact of SARS-CoV-2 infection on pregnant women and pregnancy outcome. In addition, some studies have described pathological changes in the placental tissue of SARS-CoV-2-positive mothers, which are related or not to the infection severity and/or infection trimester. Among the various molecules involved in the normal structure and functionality of the placenta, sialic acids (Sias) seem to play an important role. Hence, we aimed to investigate possible changes in the distribution and content of Sias with different glycosidic linkages, namely α2,3 and α2,6 Galactose- or N-acetyl-Galactosamine-linked Sias and polymeric Sia (PolySia), in placentas from pregnant women infected by SARS-CoV-2 during the three different pregnancy trimesters. METHODS: α2,3 and α2,6 Galactose-linked Sias were evaluated by lectin histochemistry (Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA), respectively), while immunohistochemistry was used for PolySia detection. RESULTS: Data showed lower levels of α2,3 Galactose-linked Sias in the trophoblast and underlying basement membrane/basal plasma membrane in placentas from women infected during the second and third infection trimester compared with uninfected cases and those infected during first trimester. On the other hand, higher levels of PolySia were detected in the trophoblast during the second and third infection trimester. CONCLUSIONS: Our findings suggest that changes in the sialylation status of trophoblast and its basement membrane/basal plasma membrane, together with other concomitant factors, could be at the basis of the most common placental histopathological alterations and gestational complications found especially in pregnancies with SARS-CoV-2 infection during the second and third trimester.


Assuntos
COVID-19 , Placenta , Gravidez , Feminino , Humanos , Placenta/metabolismo , COVID-19/patologia , SARS-CoV-2 , Galactose/metabolismo , Aglutininas/metabolismo
17.
Biology (Basel) ; 12(2)2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36829453

RESUMO

During pregnancy, SARS-CoV-2 infection is associated with several adverse outcomes, including an increased risk of pre-eclampsia, preterm delivery, hypertensive disorders, gestational diabetes, and fetal growth restriction related to the development of placenta vascular abnormalities. We analyzed human placenta from full-term, uncomplicated pregnancies with SARS-CoV-2 infection during the first, second, or third trimesters of gestation. We studied, by the immunohistochemistry technique, the expression of CD34 and podoplanin (PDPN) as markers of vasculogenesis to find any differences. As secondary outcomes, we correlated maternal symptoms with placental histological alterations, including fibrin deposits, lymphocyte infiltration in the villi, edema, and thrombi. Our results showed a PDPN expression around the villous stroma as a plexiform network around the villous nucleus of fetal vessels; significant down-regulation was observed in the villous stroma of women infected during the third trimester. CD34 showed no changes in expression levels. During SARS-CoV-2 infection, the most common maternal symptoms were fever, anosmia, ageusia and asthenia, and the majority were treated with paracetamol, corticosteroids and azithromycin. Patients that required multiple symptomatic treatments evidenced a large amount of fibrin deposition in the villi. Certainly, PDPN plays a key role in healthy placental vasculogenesis and thus in its proper physiology, and SARS-CoV-2 surely alters its normal expression. Further studies are necessary to understand what mechanisms are being altered to try to avoid possible complications for both the mother and fetus in terms of the contagions that will still occur.

18.
AIDS ; 37(4): 561-570, 2023 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-36504092

RESUMO

OBJECTIVE: Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report significant weight gain among persons receiving INSTI-based ART regimens compared with other regimens. DESIGN: In-vitro model of adipogenesis. METHODS: We used 3T3-L1 cells to investigate the effects of the nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with INSTIs: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG), and bictegravir (BIC) on adipose differentiation. To monitor adipocyte differentiation, expression levels of PPARÉ£ and C/EBPα and the intracellular lipid accumulation by Red Oil staining were used. Furthermore, we evaluated the immunohistochemical expression of ER-TR7, a fibroblastic marker, after INSTIs treatment. RESULTS: Compared with control, INSTIs were able to increase adipogenesis, especially RAL and ELV. TAF and TDF inhibited adipogenesis alone and in combination with INSTIs. This ability was more evident when TAF was used in combination with DTG and BIC. Finally, INSTIs increased the expression of ER-TR7 compared with control and cells treated with TAF or TDF. CONCLUSION: Our data support the evidence that in-vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used whereas TAF and TDF have an antagonistic role on this phenomenon.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Camundongos , Animais , Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Células 3T3-L1 , Adenina/uso terapêutico , Raltegravir Potássico/uso terapêutico , Diferenciação Celular , Adipócitos , Integrases/uso terapêutico
19.
J Cell Biochem ; 113(11): 3446-54, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22678819

RESUMO

The highly active antiretroviral therapy (HAART) can cause a metabolic syndrome consisting of lipodystropy/lipoatrophy, dyslipidemia, and type 2 diabetes mellitus with an increased cardiovascular risk. The pathogenetic bases of HAART-associated lipodystrophy are poorly known. A genetic screen was used to evaluate proteins that are modulated in HIV-1-infected patients with or without lipodystrophy syndrome, that are routinely treated with HAART regimens. The most significant modulation was represented by FAP48 expression. Stable over-expression of FAP48 was able to alter, in vitro, adipogenesis, acting both on calcineurin and glucocorticoid pathways. Finally, we demonstrated that FAP48 over-expression was able to influence the capacity of some HIV drugs, Saquinavir and Efavirenz, but not Stavudine, Amprenavir, and Indinavir to inhibit adipocyte formation. In conclusion, this molecule could be a potential target for novel therapeutic approaches to the HAART related lipodystrophy in HIV patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adipócitos/efeitos dos fármacos , Síndrome de Lipodistrofia Associada ao HIV/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adipócitos/metabolismo , Adipócitos/patologia , Alcinos , Animais , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Benzoxazinas/efeitos adversos , Benzoxazinas/farmacologia , Calcineurina/genética , Calcineurina/metabolismo , Carbamatos/efeitos adversos , Carbamatos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Ciclopropanos , Furanos , Expressão Gênica/efeitos dos fármacos , Glucocorticoides/metabolismo , HIV-1/efeitos dos fármacos , HIV-1/fisiologia , Síndrome de Lipodistrofia Associada ao HIV/induzido quimicamente , Humanos , Indinavir/efeitos adversos , Indinavir/farmacologia , Camundongos , Saquinavir/efeitos adversos , Saquinavir/farmacologia , Transdução de Sinais/efeitos dos fármacos , Estavudina/efeitos adversos , Estavudina/farmacologia , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia , Transfecção
20.
Artigo em Inglês | MEDLINE | ID: mdl-35270606

RESUMO

Background: Postural stability and plantar pressure parameters can be assessed by baropodometry; nevertheless, they are often affected by low repeatability. The aim of the study was to test the accuracy and repeatability of a novel resistive sensor pressure plate and to establish the most reliable baropodometric parameters. Methods: Accuracy and repeatability of the FM12050 BTS-Bioengineering plate measurements were assessed by using different weights in static conditions across three sessions. Subsequently, 20 healthy subjects were assessed by 30-s stabilometric analysis in bipedal standing with open eyes across four trials in two sessions, morning and afternoon. Results: Pressure plate repeatability in measuring the static weights was very high, and plate measurements were correlated to the scale measurements (Pearson's coefficient = 0.99). Percentage of load distribution between left and right foot and in rearfoot and forefoot regions showed the largest repeatability (coefficient of variation < 5%) across trials. Eventually, median and percentiles (25−75%) were reported for each parameter. Conclusions: This study helped to assess the accuracy and repeatability of a novel pressure plate in static conditions and to define the most reliable parameters for the assessment of postural stability and foot morphology. The present healthy-subject stabilometric dataset may be used as reference data in the evaluation of pathological populations.


Assuntos
, Extremidade Inferior , Voluntários Saudáveis , Humanos , Equilíbrio Postural
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