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Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

Chinese Journal of Integrative medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo Garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha Oliveira Gustavo JS Pereira Claudia Bincoletto Department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group on Phytocomplexes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil Department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(P<0.05).The viability of HEAV-treated K562 cells was reduced compared to HEAV-exposed fibroblasts(P<0.05).Treatment of K562 cells with HEAV induced cell death primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(P<0.05).The use of Nec-1 and Fer-1 increased the viability of K562 cells treated with HEAV relative to cells exposed to HEAV alone(P<0.01).HEAV-induced Ca^(2+)release mainly from lysosomes in K562 cells(P<0.01).Furthermore,BAPTA-AM,an intracellular Ca^(2+)chelator,decreased the number of non-viable cells treated with HEAV(P<0.05).Conclusions HEAV is cytotoxic and activates several modalities of cell death,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

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Surgical Outcomes of a Small Incision Limbus-Based Revision for Failed Trabeculectomies

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Open Journal of Ophthalmology 2022年第1期12卷 121-127页

作者： Marcus Suehiro Fabio Luis de Arruda Zantut Flavio Siqueira Lopes Michele Ushida Barbosa Syryl Dorairaj Tiago Santos Prata paulista school of medicine Federal University of Sao Paulo Sao Paulo Brazil

Background: Trabeculectomy does not always work as long as necessary to control glaucoma. This study aimed to describe the initial outcomes of a surgical technique for restoring failed trabeculectomies. Methods: We reviewed patients with failed trabeculectomy with mitomycin (MMC) who underwent limbus-based revision. After the dissection of the subconjunctival area through a smaller incision (3 mm), MMC was applied and episcleral fibrosis was excised. Each criterion was classified as complete or qualified for glaucoma medication. Results: Nineteen patients (19 eyes) were included in this study. The mean follow-up was 9.4 ± 8.6 months. At the last follow-up visit, the mean intraocular pressure was reduced from 20.9 ± 8.4 (range, 12 - 44 mmHg) to 11.6 ± 3.6 mm Hg (range, 6 - 19 mmHg) (p Conclusions: Our initial results suggest that limbus-based revision is an effective alternative to restoring failed trabeculectomies with minor postoperative complications.

关键词： Glaucoma Surgery Trabeculectomy Revision Mitomycin

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Effects of acupuncture and moxa treatment in patients with semen abnormalities

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Asian Journal of Andrology 2003年第4期5卷 345-348页

作者： Edson Gurfinkel Agnaldo P.Cedenho Ysao Yamamura Miguel Srougi Human Reproduction Division Discipline of Urology Sao Paulo Federal University Paulista School of Medicine Sao Paulo BrazilHuman Reproduction Division Discipline of Urology Sao Paulo Federal University Paulista School of Medicine Sao Paulo BrazilHuman Reproduction Division Discipline of Urology Sao Paulo Federal University Paulista School of Medicine Sao Paulo BrazilHuman Reproduction Division Discipline of Urology Sao Paulo Federal University Paulista School of Medicine Sao Paulo Brazil

Aim: To evaluate the effect of Chinese Traditional medicine, acupuncture and moxa treatment, on the semen quality in patients with semen abnormalities. Methods: In a prospective, controlled and blind study, nineteen patients, aged 24 years-42 years and married for 3 years-11 years without children with semen abnormalities in concentration, morphology and/or progressive motility without apparent cause, were randomized into two groups and submitted to acupuncture and moxa treatment at the therapeutic (Study Group) and the indifferent points (Control Group), respectively, for 10 weeks. Semen analyses were performed before and after the treatment course. Results: The patients of the Study Group presented a significant increase in the percentage of normal-form sperm compared to the Control Group (calculated U=16.0, critical U=17.0). Conclusion: The Chinese Traditional medicine acupuncture and moxa techniques significantly increase the percentage of normal-form sperm in infertile patients with oligoastenoteratozoospermia without apparent cause.

关键词： acupuncture Chinese traditional medicine infertility moxibustion oligozoospermia teratozoospermia semen

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Congenital heart diseases trends in S?o Paulo State,Brazil:a national live birth data bank analysis

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World Journal of Pediatrics 2022年第7期18卷 472-481页

作者： Paola Soares Fernandes Larissa Rosario Magalhaes Tainara Rita Pezzini Edige Felipe de Sousa Santos Mauricio Giusti Calderon Medical school Nine of July University(Uni9).Sao Bernardo do CampoSPBrazil Epidemiology Department Public Health SchoolSao Paulo University(USP)Sao PauloSPBrazil Pediatric Surgery Department Hospital Benficencia Portuguesa de Sao PauloRua Maestro Cardim768Sao PauloSP CEP 01323-011Brazil Pediatric Surgery Department Hospital Santa Catarina PaulistaAv.Paulista200.Sao PauloSP CEP:01310-000Brazil

Background Congenital heart diseases(CHD)are the most common type of birth defects,affecting millions of newborns every year;no prevalence data are available in S?o Paulo State,Brazil's most populous *** objective is to identify trends in prevalence and risk factors for CHD in Sao Paulo State,*** We developed a population-based study to estimate the CHD trend of prevalence in recent years,stratified by maternal age and geographical clusters,using all cases of CHD identified by the Live Births Information System(SINASC-Sistema de Informa??o Sobre Nascidos Vivos)from January 1,2005,to December 31,*** calculated the trends of prevalence,the regression coefficient(β),the annual percent change(APC),and 95%confidence interval using the Prais-Winsten regression model,with the Durbin-Watson *** We found 10,594 cases of CHD among 8,536,101 live births(LB),a prevalence of 12.4/10,000 *** was no difference in the sex distribution;they are primarily Caucasian(60.2%),75.2%born at term,and 74.4%weight>2500 g,66.9%of births were by cesarean section.S?o Paulo State presented an increasing CHD trend of prevalence(APC=18.9%).The highest CHD prevalence rate was in mothers aged≥35 years(22.2/10,000 LB).There were 12,271 specific congenital heart defects among 10,594 patients(1.16 CHD/patient).Atrial septal defect has the highest number of cases(3835),with a prevalence of 4.49/10,000 LB,corresponding to 31.3%of all *** CHD had an increasing prevalence trend in recent years,being highest in S?o Paulo City and≥35-year mothers.

关键词： Congenital abnormalities Epidemiology Heart defects Interrupted time series PrevalencePublic health

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Role of Selective Cyclo-Oxygenase-2 Inhibitor Celecoxib in Canine Osteosarcoma Cell Culture

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Open Journal of Pathology 2013年第4期3卷 144-149页

作者： Paulo R.O.Bersano Maria T.S.Alves Maria F.M.R.Gartner Adriana Camargo Ferrasi Joao F.Lima-Neto Fernanda C.Landim Stephane C.Vexenat Carlos Eduardo Fonseca Alves Glenda Nicioli da Silva Noeme S.Rocha Laboratory of Investigative and Comparative Pathology School of Veterinary Medicine and Animal ScienceUniversidade Estadual PaulistaBotucatuBrazil Department of Pathology Paulista School of MedicineFederal University of Sao PauloSao PauloBrazil Institute of Molecular Pathology and Immunology of University of Porto PortoPortugal hemocentro paulista school of medicine Federal University of Sao PauloSao PauloBrazil Laboratory of Reproduction and Cellular Therapy Department of Animal Reproduction and Veterinary RadiologyUniversidade Estadual PaulistaBotucatuBrazil

Background: Experimental studies have shown that cyclo-oxygenase-2 (Cox2) is related to the development and progression of tumors, since this enzyme is induced and expressed by cells such as macrophages, osteoblasts, “activated” endothelial cells, and tumor cells. The activity in tumors includes proliferation, cell transformation, tumor growth, invasion and metastasis and may play an important role in carcinogenesis of the canine osteosarcoma, since it has high expression in tissue fragments. The combination of selective Cox2 inhibitors and other treatment modalities is the basis for a new anti-cancer therapy strategy. This in vitro study exposed primary cells of five different canine osteosarcoma cultures to selective Cox2 inhibitor at increasing concentrations and times. Results: For Cox2 negative cultures, despite the absence of differences, greater sensitivity of cells to treatment was observed. For Cox2 positive cultures, a higher number of necrotic cells were observed (P ≤ 0.05), when compared with negative cultures. For exposure times with Celecoxib doses, no difference (P > 0.05) was found between the three times analyzed for living, apoptotic and apoptotic/necrotic cells. There are similarities in the values of 24 h and 48 h, with slight reduction of living cells, increasing those undergoing apoptosis and apoptosis/necrosis. There was significance for necrosis (P ≤ 0.05). In 72 hours, a significant difference was observed between the other two previous values (P ≤ 0.05). It was found for the group of 100 μML-1, that there was a numerically greater signaling for apoptosis and lower (P = 0.08) for necrosis, and this point was the onset of the pharmacodynamic phenomenon, with drop in the values for living cells and increased number of necrotic cells, with a tendency (P = 0.08) for reducing the percentage of necrotic cells for the group of 100 μML-1 when compared to that of 10 μML-1. Conclusions: For Cox2 positive and negative cultures, there was difference for

关键词： Canine Osteosarcoma Cyclo-Oxygenase-2 Celecoxib

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Approach to Pain in Endometriosis Patients: Systematic Literature Review

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Journal of Biosciences and medicines 2022年第11期10卷 1-27页

作者： Vanessa Ferreira Dias Duarte da Costa Maria Eduarda Pazini Modesto Gonçalves Camila dos Santos Leite Oscar César Pires Laboratory of Pharmacology and Physiology Medicine Department Taubaté University Taubaté Brazil Laboratory of Immunopharmacology and Molecular Biology S&atilde o Francisco University Medical school Bragan&ccedil a paulista Brazil

Background: Endometriosis is a gynecological, multifactorial condition that affects women’s life quality, especially due to the pain inherent to it. Pain is caused by physical and psychological aspects;therefore, several factors must be analyzed, aiming to treat the whole. Conventional, drug or surgical treatments are the most used;however, the search for alternative therapeutic methods is growing. Objective: To analyze the approach to pain in women with endometriosis, seeking a better understanding of the pathophysiological mechanisms of this disease, its impact on life quality, as well as the means of treatments in use and innovations in this field. Methods: Systematic literature review, conducted in the Virtual Health Library databases between 2010 and 2021, restricted to articles in English and Portuguese with the descriptors: Endometriosis, Pain, and Treatment. After reading the abstracts, 197 articles were found, and, after reading them, 59 articles were selected. Results: This review analyzed 59 scientific studies that rigorously met the previously established characteristics in the sample selection. The synthesis included the following aspects: author/year of publication, article title, objective, type of study and database. Related factors such as acute or chronic pain, late diagnosis, discrediting symptomatic complaints and trivialization by health professionals have a profound impact on the physical and mental health of women with endometriosis. On the other hand, there are several classes of drugs, surgical procedures, and alternative therapies available for pain management. Conclusion: Given the context addressed, a certain need is suggested for health professionals to better understand the disease and adopt new behaviors or improve existing ones, such as reception, active listening, early diagnosis and comprehensive and individualized treatment. In addition, further studies are needed regarding alternative therapies, seeking to expand the scientific ev

关键词： Endometriosis Pain Treatment

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Tracheal Intubation Difficulties: Systematic Literature Review

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Journal of Biosciences and medicines 2022年第5期10卷 95-104页

作者： Vanessa Ferreira Dias Duarte da Costa Mariana Ronchesel Barauna Camila dos Santos Leite Oscar César Pires Laboratory of Pharmacology and Physiology Medicine Department Taubaté University Taubaté Brazil Laboratory of Immunopharmacology and Molecular Biology S&atilde o Francisco University Medical school Bragan&ccedil a paulista Brazil

Background: Tracheal intubation is a common procedure in medical practice, being performed mainly in surgical centers and emergencies in trauma patients. Objective: This systematic literature review aims to understand the main difficulties and complications related to tracheal intubation. Methods: Systematic literature review, conducted in the Virtual Health Library databases between 2016 and 2021, restricted to articles in English and Portuguese with the descriptors: Airway, Difficult intubation, and Complications. After reading the abstracts, 34 articles were found, and, after reading them, 9 articles were selected. Results: This review analyzed 9 scientific studies that rigorously met the previously established characteristics in the sample selection. The synthesis included the following aspects (author/year of publication, article title, objective, type of study, and database. Discussion: Several factors that influence the success of intubation were identified, such as technical, professional, and patient issues. In addition, measures to minimize the risks involving the procedure were highlighted. Conclusion: Tracheal intubation is a common procedure in surgical centers and emergencies. However, its risks, while low, should not be ignored. Unsuccessful procedures can occur and have consequences for the patient, such as trauma to the upper airway.

关键词： Airway Difficult Intubation Complications

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Effects of Ketoprofen, Ketamine, Lidocaine and Propofol on Fentanyl-Induced Hyperalgesia in Rats

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Journal of Biosciences and medicines 2022年第7期10卷 53-63页

作者： Camila dos Santos Leite Naira Correia Cusma Pelógia Eliane Stevanato Marília Hidalgo Uchôas Gabriela Apóstulo Silva Guilherme Apóstulo Silva Carlos Augusto Pires Zerbini Marta Helena Rovani Pires Oscar César Pires Laboratory of Immunopharmacology and Molecular Biology S&atilde o Francisco University Medical school Bragan&ccedil a paulista Brazil Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds S&atilde o Francisco University Medical school Bragan&ccedil a paulista Brazi Laboratory of Pharmacology and Physiology Medicine Department Taubaté University Taubaté Brazil Vera Cruz Hospital Campinas Brazil

Opioid-induced hyperalgesia negatively affects physiological pain management and presents a complex causal mechanism, involving, pharmacodynamic and pharmacokinetic factors of interactions with receptors, opioid-independent ascending systems and with pro-nociceptive systems. After approval by the CEUA, 42 male Wistar rats were divided into 7 groups: In group 1 (GCSSL) the animals received 1 ml of 0.9% saline solution intraperitoneally (IP);in group 2 (GFTSL), they received fentanyl at a dose of 100 ug·kg-1 IP;in the remaining groups (3, 4, 5, 6 and 7) the animals received IP, fentanyl at a dose of 100 ug·kg-1 followed also by IP route of: group 3 (GFTKP) ketoprofen at a dose of 5 mg·kg-1;group 4 GFTKT), ketamine up to a dose of 10.0 mg·kg-1;group 5 (GFTLI), incisional lidocaine up to a dose of 10 mg·kg-1;group 6 (GFTLP), intraperitoneal lidocaine up to a dose of 10 mg·kg-1 and group 7 (GFTPP), propofol up to a dose of 60 mg·kg-1. Under general anesthesia, all animals with a plantar surgical incision. Hyperalgesia was evaluated by applying Von Frey filaments on the 2nd, 1st, 3rd and 5th days after treatment. In the 2nd hour and on the 5th day after the procedure, there was no hyperalgesia associated with the use of fentanyl, however, on the 1st and 3rd postoperative days there was hyperalgesia that was attenuated by ketoprofen, ketamine, lidocaine infiltrated in the incision and intraperitoneally, an effect not observed with the use of propofol. The results suggest fentanyl-induced hyperalgesia and the efficacy of ketoprofen, ketamine, incisional lidocaine and intraperitoneal lidocaine in reducing this effect.

关键词： Hyperalgesia Fentanyl Ketoprofen Ketamine Lidocaine Propofol Rats

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New Screening Approach for Ocular Diseases

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Health 2023年第10期15卷 1059-1069页

作者： Rogil José De Almeida Torres Andréa Luchini Rogério João De Almeida Torres Mebaliah Luchini De Almeida Torres Lucas Antônio De Almeida Torres Department of Medical Clinic Medical School Universidade Estadual Paulista (UNESP) Botucatu SP Brazil

Objective: Present a new screening approach for ocular diseases. Method: Transversal, retrospective, single center study that analyzed medical records of patients from a social project on the prevention of blindness and amblyopia, which aimed at: 1) Detect the main ocular disorders such as amblyopia, primary angle-closure suspect (PACS);glaucoma suspect (GS);predisposing retinal detachment lesions (PRDL);age-related macular degeneration (AMD), and diabetic retinopathy (DR);2) Perform cataract diagnosis;3) Provide guidance and treatment for allergic conjunctivitis. 4) Prescribe glasses for children until 14 years of age. Participants were examined by a single specialist, holder of a post-doctoral degree in ophthalmology, with 36 years of experience and a sub-specialization in retina and vitreous. All data were analyzed in 2022. Results: The examiner diagnosed 42 cases of PACS, 21 of GS, 8 of PRDL, 14 of AMD, 3 of DR, 40 of cataract and 31 cases of allergic conjunctivitis. Thirty-three participants younger than 14 were prescribed glasses. Other pathologies included retinal detachment, papilledema, corneal ulcer, suspected conjunctival squamous cell carcinoma, retinal vasculitis, strabismus, uveitis, bilateral papilla paleness and lacrimal duct obstruction. Out of the 297 cases examined, 168 participants presented some type of alteration that could compromise their vision. Conclusion: The examiner’s experience and knowledge were decisive factors for the quick diagnosis, advice, screening and/or treatment of several ocular diseases. The social project results reveal that the primary care and/or the screening performed by a specialist are likely to reduce blindness cases.

关键词： Screening Ocular Diseases Primary Prevention Secondary Prevention Health Care Quality Access Evaluation Amaurosis

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Medical school Students’ Knowledge of Pain and Palliative Care: An Observational Study

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Journal of Biosciences and medicines 2023年第4期11卷 39-49页

作者： Carolina Koutras Jacob Marina Perini Carlos Augusto P. Zerbini Marta H. R. Pires Camila Dos Santos Leite Oscar César Pires Laboratory of Pharmacology and Physiology Medicine Department Taubaté University Taubaté Brazil Vera Cruz Hospital Campinas Brazil Laboratory of Immunopharmacology and Molecular Biology S&atildeo Francisco University Medical School Bragan&ccedila Paulista Brazil Laboratory of Cell and Molecular Tumor Biology and Bioactive Compounds S&atildeo Francisco University Medical School Bragan&ccedila Paulista Brazil

Background: Pain and palliative care are a reality in daily routines of medical treatment. However, the theoretical-practical curricula of traditional medical school course still unsatisfactorily contemplate pain management, as well as the palliative care approach. Objective: To assess the knowledge of medical students about pain and palliative care, as well as to identify their perception of teaching these topics during hospitalization. Methods: A cross-sectional observational study, with a descriptive and exploratory approach, data collection for which was carried out between August and November 2020. The target population was medical students, who responded to an online survey of a quantitative, anonymous and follow-up nature. The survey study variables concerned knowledge about pain management and palliative care. Results: An expressive majority of academics showed difficulty in understanding the pathophysiology of pain related to prescribing drugs for pain management purposes, and all of them believe that it is necessary to acquire more knowledge about pain treatment. In parallel, only 9.3% report having received sufficient information regarding palliative care during medical school. Conclusion: The results suggest a certain lack of knowledge and insecurity among medical school students with respect to pain management and care for patients receiving palliative care. The didactical approach to this theme is still deficient in the medical curriculum and requires immediate improvement and new proposals that address the training of these professionals in a more specific and effective way.

关键词： Pain Palliative Care Medical Students Academic Institutions

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