Physical Exercise for Treating the Anxiety and Depression Symptoms of Parkinson's Disease: Systematic Review and Meta-Analysis.

BACKGROUND: Depression and anxiety are non-motor symptoms of Parkinson's disease (PD). Physical exercise is a promising approach to reducing neuropsychological burden. We aimed to comprehensively synthesize evidence regarding the use of exercise for treating depression and anxiety symptoms in PD. METHODS: Systematic review and meta-analysis following PRISMA recommendations. Searches on PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Physiotherapy Evidence Database (PEDro) was conducted. The random-effects model was employed for all analyses with the standardized mean difference as the effect estimate. RESULTS: Fifty records were retrieved, but only 17 studies met the criteria for the meta-analyses. A moderate to large effect was observed for depression (-.71 [95% CI = -.96 to -.46], 11 studies, 728 individuals), and a small to moderate effect for anxiety (-.39 [95% CI = -.65 to -.14], 6 studies, 241 individuals), when comparing exercise to non-exercise controls. Subgroup analysis revealed significant effects from aerobic (-.95 [95% CI = -1.60, -.31]), mind-body (-1.85 [95% CI = -2.63, -1.07]), and resistance modalities (-1.61 [95% CI = -2.40, -.83]) for depression, and from mind-body (-.67 [95% CI = -1.19 to -.15]) and resistance exercises (-1.00 [95% CI = -1.70 to -.30]) for anxiety. CONCLUSION: Physical exercise has a relevant clinical impact on depression and anxiety in PD. We discuss the level of the evidence, the methodological limitations of the studies, and give recommendations.

Physical exercise for treating non-motor symptoms assessed by general Parkinson's disease scales: systematic review and meta-analysis of clinical trials.

Introduction: Parkinson's disease is a movement disorder that also manifests non-motor symptoms (NMS). Physical exercise is a prominent strategy that can have an impact on NMS; however, the evidence is limited. Our aim was to verify the effects of exercise on NMS, as assessed using general NMS scales. Methods: This study is a systematic review and meta-analysis. Two searches were conducted on the PubMed, Cochrane Library, Scopus, Web of Science, Embase, Science Direct and PEDro databases from September to December 2022. The PEDro scale was used to assess the methodological quality of the studies. Results: Twenty-three studies were included. The interventions were classified as multimodal, aerobic, resistance, dance, conventional physical therapy and other types. Five studies had high risk of bias. Eight studies were included in the meta-analyses. According to the criteria, four studies compared exercise with non-exercise (n=159), two compared multimodal exercise with cognitive/leisure approaches (n=128), and two compared aerobic with conventional exercise (n=40). No statistical differences were observed between exercise and non-exercise (-0.26 (-0.58 to 0.05)) and between multimodal and cognitive approaches (0.21 (-0.14 to 0.55)). However, trends were observed in the direction of exercise and cognitive approaches. A significant difference was observed favouring aerobic over conventional exercise (-0.72 (-1.36 to -0.08)). Conclusions: Our findings suggest that exercise may have an effect on general NMS compared with non-exercise, although only a trend was observed. It was also observed for cognitive approaches over multimodal exercises. Aerobic exercise showed near-large effects compared with conventional exercise.

Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction.

Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1ß were observed in Sevo, increases in IL-1ß in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.

Dipotassium Glycyrrhizininate Improves Skin Wound Healing by Modulating Inflammatory Process.

Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (Tnf-α, Cox-2, Il-8, Irak-2, Nf-kB, and Il-1) while increasing the expression of Il-10, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.

Comparison of muscular activity on ergometric bicycle and elliptical trainer in subjects with incomplete spinal cord injury / Comparação da atividade muscular em bicicleta ergométrica e aparelho elíptico em indivíduos com lesão medular incompleta

Abstract Introduction Spinal cord injury generates muscle weakness, impairing orthostatism and gait. The elliptical trainer (ET) and the ergometric bicycle (EB) are rehabilitation options for this subject. Understanding the pattern of muscle activation generated by these methods is important to answer questions arising from clinical practice. Objective To verify muscle activation with ET and EB with and without electromyographic biofeedback in subjects with incomplete spinal cord injury (ISCI). Methods Cross-sectional crossover study, enrolled in Clinical Trials (NCT05118971). Subjects with spinal cord injury (incomplete spinal cord injury group - ISCIG) and without spinal cord injury (reference group - RG) were randomized into four groups: elliptical group (EG), elliptical + biofeedback group (EBG), bicycle group (BG) and bicycle + biofeedback group (BBG). Subjects were assessed for functionality by the Functional Independence Measure, injury classification by the ASIA Scale, muscle tone by the modified Ashworth scale, and muscle activity by electromyography. Results There was greater activation of the tibialis anterior on cycling compared to other modalities in ISCIG. Biofeedback offered no difference in any of the groups. In RG the vastus medialis was the most activated muscle in all modalities, with more expressive activation in the ET. In this same group, the tibialis anterior was more activated on the EB. Conclusion This study showed that both ET and EB are safe and effective in recruiting the muscles investigated, encouraging its use by rehabilitation professionals when the objective is to strength muscles involved in gait.

Resumo Introducão A lesão medular gera fraqueza muscular, preju-dicando o ortostatismo e a marcha. O aparelho elíptico (EL) e a bicicleta ergométrica (BE) são opções de reabilitação para estes sujeitos. Compreender o padrão de ativação muscular gerado por esses métodos é importante para esclarecer dúvi-das advindas da prática clínica. Objetivo Verificar a ativação muscular com EL e BE com e sem biofeedback eletromiográfico em indivíduos com lesão medular incompleta (LMI). Métodos Estudo transversal do tipo crossover, inscrito no Clinical Trials (NCT05118971). Sujeitos com lesão medular (grupo lesão medular incompleta - GLMI) e sem lesão medular (grupo refe-rência - GR) foram randomizados em quatro grupos: elíptico (GE), elíptico + biofeedback (GEB), bicicleta (GB) e bicicleta + biofeedback (GBB). Os indivíduos foram avaliados quanto à funcionalidade pela Medida de Independência Funcional, classificação da lesão pela Escala ASIA, tônus muscular pela escala modificada de Ashworth e atividade muscular por eletromiografia. Resultados Houve maior ativação do tibial anterior no ciclismo em comparação com outras modalidades no GLMI. O biofeedback não ofereceu nenhuma diferença em nenhum dos grupos. No GR, o vasto medial foi o músculo mais ativado em todas as modalidades, com ativação mais expressiva no EL. Neste mesmo grupo, o tibial anterior foi mais ativado na BE. Conclusão Este estudo mostrou que tanto o EL quanto a BE são seguros e eficazes no recrutamento dos músculos investigados, incentivando seu uso por profissionais da reabilitação quando o objetivo é fortalecer os músculos envolvidos na marcha.

A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease.

BACKGROUND: Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão. METHODS: A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67. RESULTS: Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients' survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank). CONCLUSIONS: Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.

Anti-Migratory Effect of Dipotassium Glycyrrhizinate on Glioblastoma Cell Lines: Microarray Data for the Identification of Key MicroRNA Signatures.

The nuclear factor kappa B (NF-κB) pathway has been reported to be responsible for the aggressive disease phenomenon observed in glioblastoma (GBM). Dipotassium glycyrrhizinate (DPG), a dipotassium salt of glycyrrhizic acid isolated from licorice, has recently demonstrated an anti-tumoral effect on GBM cell lines U87MG and T98G through NF-κB suppression by IRAK2- and TRAF6-mediating microRNA (miR)-16 and miR-146a, respectively. Thus, the present study aimed to evaluate the expression profiles of miRNAs related to NF-κB suppression in T98G GBM cell line after DPG exposure using miRNA microarray (Affymetrix Human miRNA 4.0A), considering only predicted miRNAs as NF-κB regulator genes. Additional assays using U251 and U138MG cells were performed to validate the array results. DPG cytotoxicity was determined by (4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and cellular apoptosis was quantified by DNA fragmentation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The anti-proliferative effect was observed by cell proliferation and wound-healing assays, and the sphere formation assay examined whether DPG reduced stem cell subpopulation formation. The most over-expressed miRNAs were miR-4443 and miR-3620. The cytotoxic effect of DPG in U251 and U138MG was observed with an IC50 of 32 and 20 mM for 48 h, respectively. The IC50 of each cell line was used in all further assays. DPG treatment-induced apoptosis is observed by DNA fragmentation and increased TUNEL-positive cells. Cell proliferation and wound-healing assays showed an anti-proliferative and anti-migratory effect by DPG on the evaluated cell lines. In addition, DPG treatment led to a 100% reduction in sphere formation. The qPCR results in U251 and U138MG cells showed that DPG increased miR-4443 (2.44 vs. 1.11, p-value = 0.11; 8.27 vs. 1.25, p-value = 0.04) and miR-3620 expression (1.66 vs. 1.00, p-value = 0.03; 8.47 vs. 1.01, p-value = 0.03) and decreased CD209 (0.44 vs. 1.10, p-value = 0.03; 0.49 vs. 1.07, p-value = 0.04) and TNC (0.20 vs. 1.03, p-value = 0.001; 0.39 vs. 1.06, p-value = 0.01) mRNA levels compared to controls. Our results suggest that DPG inhibits cell viability by activating apoptosis and inhibiting cell proliferation and stem cell subpopulation formation through miR-4443 and miR-3620 upregulation. Both miRNAs are responsible for the post-transcriptional inhibition of NF-κB by CD209 and TNC modulation.

Dipotassium Glycyrrhizinate on Melanoma Cell Line: Inhibition of Cerebral Metastases Formation by Targeting NF-kB Genes-Mediating MicroRNA-4443 and MicroRNA-3620-Dipotassium Glycyrrhizinate Effect on Melanoma.

Glycyrrhizic acid (GA), a natural compound isolated from licorice (Glycyrrhiza glabra), has exhibited anti-inflammatory and anti-tumor effects in vitro. Dipotassium glycyrrhizinate (DPG), a dipotassium salt of GA, also has shown an anti-tumor effect on glioblastoma cell lines, U87MG and T98G. The study investigated the DPG effects in the melanoma cell line (SK-MEL-28). MTT assay demonstrated that the viability of the cells was significantly decreased in a time- and dose-dependent manner after DPG (IC50 = 36 mM; 24 h). DNA fragmentation suggested that DPG (IC50) induced cellular apoptosis, which was confirmed by a significant number of TUNEL-positive cells (p-value = 0.048) and by PARP-1 [0.55 vs. 1.02 arbitrary units (AUs), p-value = 0.001], BAX (1.91 vs. 1.05 AUs, p-value = 0.09), and BCL-2 (0.51 vs. 1.07 AUs, p-value = 0.0018) mRNA compared to control cells. The proliferation and wound-healing assays showed an anti-proliferative effect on DPG-IC50-treated cells, also indicating an inhibitory effect on cell migration (p-values < 0.001). Moreover, it was observed that DPG promoted a 100% reduction in melanospheres formation (p-value = 0.008). Our previous microRNAs (miRs) global analysis has revealed that DPG might increase miR-4443 and miR-3620 expression levels. Thus, qPCR showed that after DPG treatment, SK-MEL-28 cells presented significantly high miR-4443 (1.77 vs. 1.04 AUs, p-value = 0.02) and miR-3620 (2.30 vs. 1.00 AUs, p-value = 0.01) expression compared to control cells, which are predicted to target the NF-kB, CD209 and TNC genes, respectively. Both genes are responsible for cell attachment and migration, and qPCR revealed significantly decreased CD209 (1.01 vs. 0.54 AUs, p-value = 0.018) and TNC (1.00 vs. 0.31 AUs, p-value = 2.38 × 10−6) mRNA expression levels after DPG compared to untreated cells. Furthermore, the migration of SK-MEL-28 cells stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA) was attenuated by adding DPG by wound-healing assay (48 h: p-value = 0.004; 72 h: p-value = 7.0 × 10−4). In addition, the MMP-9 expression level was inhibited by DPG in melanoma cells stimulated by TPA and compared to TPA-treated cells (3.56 vs. 0.99 AUs, p-value = 0.0016) after 24 h of treatment. Our results suggested that DPG has an apoptotic, anti-proliferative, and anti-migratory effect on SK-MEL-28 cells. DPG was also able to inhibit cancer stem-like cells that may cause cerebral tumor formation.

Non-Coding RNA in Penile Cancer.

Penile cancer (PC) still presents a health threat for developing countries, in particular Brazil. Despite this, little progress has been made on the study of markers, including molecular ones, that can aid in the correct management of the patient, especially concerning lymphadenectomy. As in other neoplasms, non-coding RNAs (ncRNAs) have been investigated for penile cancer, with emphasis on microRNAs, piRNAs (PIWI-interacting small RNAs), and long non-coding RNAs (LncRNAs). In this context, this review aims to assemble the available knowledge on non-coding RNA linked in PC, contributing to our understanding of the penile carcinogenesis process and addressing their clinical relevance. ncRNAs are part of the novel generation of biomarkers, with high potential for diagnosis and prognosis, orientating the type of treatment. Furthermore, its versatility regarding the use of paraffin samples makes it possible to carry out retrospective studies.

Biochemical and Toxinological Characterization of Venom from Macrorhynchia philippina (Cnidaria, Hydrozoa).

Macrorhynchia philippina is a colonial benthic hydroid from the Class Hydrozoa (Phylum Cnidaria) distributed in the tropical and subtropical marine waters from Atlantic Ocean, Indo-Pacific, and Mozambique. Its colonies somewhat resemble plants, causing confusion in the bathers who accidentally touch the animal. Acute burning/local pain, edema, erythema, and pruritus were symptoms already described, but its venom composition is unknown, as well as the participation of toxins for the symptom's development. Thus, herein, we show the biochemical composition and toxic effects of M. philippina venom. Colonies were collected and processed for histological analysis; alternatively, they were immersed into methanol containing 0.1% acetic acid for venom attainment, which was analyzed by mass spectrometry and submitted to edema and nociception evaluation in mice, hemolysis and antimicrobial assays in vitro. Before the molecule's extraction, it was possible to see the inoculation structures (hydrocladiums and hydrotheca) containing venom, which was released after the immersion of the animal in the solvents. The venom was composed mainly by low molecular mass compounds, able to cause significant reduction of the paw withdrawal latency from the hot plate test, 30 minutes after the injection. Moreover, significant edema was observed 10 and 30 minutes after the injection, indicating the activity of at least two inflammatory mediators. The venom caused no hemolytic activity but reduced the growth of A. baumannii and K. pneumoniae strains. This study is the first biochemical description of M. philippina venom, with molecules that cause fast inflammatory and painful effects, characteristic of the envenomation.

Primary Leiomyosarcoma of the Glans.

Penile leiomyosarcoma isz an extremely uncommon entity that rarely occurs in the glans. Due to the limited number of cases described in literature, guidelines regarding non-surgical treatment, prognosis, and management remain equivocal. Among the mesenchymal tumors of the penis, leiomyosarcoma has the highest propensity for recurrence. It originates in the smooth muscle cells from two distinct locations: superficial and deep. The deep subtype is the most aggressive and has the highest potential for metastasis. Surgical treatment should be implemented early and must be locally aggressive. Herein, we present a rare case of a 54-year-old patient with deep localized leiomyosarcoma of the glans, albeit with superficial characteristics. A review of the main histopathological, clinical, immunohistochemical, and therapeutic aspects of this unusual entity is presented.

Biochemical and toxinological characterization of venom from Macrorhynchia philippina (Cnidaria, Hydrozoa)

Macrorhynchia philippina is a colonial benthic hydroid from the Class Hydrozoa (Phylum Cnidaria) distributed in the tropical and subtropical marine waters from Atlantic Ocean, Indo-Pacific, and Mozambique. Its colonies somewhat resemble plants, causing confusion in the bathers who accidentally touch the animal. Acute burning/local pain, edema, erythema, and pruritus were symptoms already described, but its venom composition is unknown, as well as the participation of toxins for the symptom’s development. Thus, herein, we show the biochemical composition and toxic effects of M. philippina venom. Colonies were collected and processed for histological analysis; alternatively, they were immersed into methanol containing 0.1% acetic acid for venom attainment, which was analyzed by mass spectrometry and submitted to edema and nociception evaluation in mice, hemolysis and antimicrobial assays in vitro. Before the molecule’s extraction, it was possible to see the inoculation structures (hydrocladiums and hydrotheca) containing venom, which was released after the immersion of the animal in the solvents. The venom was composed mainly by low molecular mass compounds, able to cause significant reduction of the paw withdrawal latency from the hot plate test, 30 minutes after the injection. Moreover, significant edema was observed 10 and 30 minutes after the injection, indicating the activity of at least two inflammatory mediators. The venom caused no hemolytic activity but reduced the growth of A. baumannii and K. pneumoniae strains. This study is the first biochemical description of M. philippina venom, with molecules that cause fast inflammatory and painful effects, characteristic of the envenomation.

Food consumption patterns, overweight and cardiovascular risk: a cross-sectional analysis of the Pró-Saúde Study, Brazil, 2013. / Padrão de consumo de alimentos, excesso de peso e risco cardiovascular: uma análise transversal do Estudo Pró-Saúde, 2013.

OBJECTIVE: To identify food consumption patterns and association between overweight and risk of cardiovascular disease. METHODS: This was a cross-sectional study with staff of the Universidade do Estado do Rio de Janeiro, Brazil, who took part in the Pró-Saúde Study. Food consumption was investigated using a food frequency questionnaire. Association between dietary patterns (exposure) and overweight and cardiovascular risk (outcomes) was estimated using linear regression. RESULTS: Among the 520 staff assessed, four dietary patterns were found: 'ultra-processed', 'healthy', 'meat' and 'traditional'. After adjustment, the 'meat' pattern was inversely associated with waist circumference (ß=-1.52 - 95%CI -2.66;-0.39), body mass index (ß=-0.56 - 95%CI -1.01;-0.11), and the Framingham Risk Score (ß=-0.36 - 95%CI -0.64;-0.09). CONCLUSION: In view of excess weight, risk of cardiovascular disease and inverse association between the 'meat' food consumption pattern and BMI, it is important to conduct further investigations, with non-working groups, with the aim of gaining greater understanding of the health-disease process related to food consumption.

Effects of dipotassium glycyrrhizinate on wound healing.

PURPOSE: Dipotassium glycyrrhizinate (DPG) has anti-inflammatory properties, besides promoting the regeneration of skeletal muscle. However, it has not been reported on skin wound healing/regeneration. This research aimed to characterize the effects of DPG in the treatment of excisional wounds by second intention. METHODS: Male adults (n=10) and elderly (n=10) Wistar rats were used. Two circular wounds were excised on the dorsal skin. The excised normal skins were considered adult (GAN) and elderly (GIN) naïve. For seven days, 2% DPG was applied on the proximal excision: treated adult (GADPG) and elderly (GIDPG), whereas distal excisions were untreated adult (GANT) and elderly (GINT). Wound healing areas were daily measured and removed for morphological analyses after the 14th and the 21st postoperative day. Slides were stained with hematoxylin-eosin, Masson's trichrome, and picrosirius red. RESULTS: Histological analysis revealed intact (GAN/GIN) and regenerated(GANT/GINT/GADPG/GIDPG) skins. No differences of wounds' size were found among treated groups. Epidermis was thicker after 14 days and thinner after 21 days of DPG administration. Higher collagen I density was found in GIDPG (14th day) and GADPG (21st day). CONCLUSIONS: DPG induced woundhealing/skin regeneration, with collagen I, being more effective in the first 14 days after injury.

Oral Conditions of Elders and Middle-aged Individuals with Multiple Myeloma.

AIM AND OBJECTIVE: The aim and objective of the present study was to assess the oral conditions of middle-aged and elderly individuals with multiple myeloma. MATERIALS AND METHODS: This cross-sectional, observational study was carried out in the city of Fortaleza, Ceará, in Northeastern Brazil. An oral examination was performed with 19 patients with multiple myeloma, and information on gender, age, diagnosis, diagnosis duration (months/years), and treatment duration (months/years) were collected. The gingival bleeding index (GBI) and probing depth (PD) were measured to check for periodontal disease, and the decayed, missing, and filled teeth (DMFT) index was used to assess dental conditions. Inferential statistics were also used, as well as the Mann-Whitney test to compare genders and continuous variables and the chi-square test for comparisons among the same groups with categorical variables. All statistical tests adopted a significance threshold of p ≤0.05. RESULTS: Among the 19 patients analyzed, 10 (52.6%) were elderly, and 9 (47.4%), middle-aged. The mean age of the participants was 63.4 ± 11.7 years, ranging from 48 to 83 years old. Statistical significance was found regarding missing teeth in the elderly group (p = 0.037), restored teeth in the middle-aged group (p = 0.029), and gingival bleeding among women (p = 0.050). Hyposalivation was observed in 89.5% of the individuals, of which 68.4% were characterized as moderate to severe. CONCLUSION: Better dental conditions were observed in the middle-aged group when compared to the elderly. Men presented the lowest GBI values. The salivary flow of patients with multiple myeloma was reduced, and most of them showed moderate to severe hyposalivation. It can be assumed that such a situation is caused by the action of drugs, chemotherapy, or even age. Improvements in the oral health of these patients are needed in order to promote a better quality of life. CLINICAL SIGNIFICANCE: Knowledge of the oral manifestations of multiple myeloma patients is essential to assist in the early diagnosis of these alterations, as well as to propose an adequate treatment plan, aiming to improve these patients' quality of life.

Neurotoxicity of Olindias sambaquiensis and Chiropsalmus quadrumanus extracts in sympathetic nervous system.

Cnidarians are equipped with nematocysts, which are specialized organelles used to inoculate venom during prey capturing and defense. Their venoms are rich in toxins and a potential source of bioactive compounds, however, poorly explored so far. In this work, the activity of the methanolic extracts from the hydromedusa Olindias sambaquiensis and the cubozoan jellyfish Chiropsalmus quadrumanus were studied in sympathetic neurotransmission. For that, bisected rat vas deferens - a classic model of sympathetic neurotransmission - were incubated with the extracts for further myographic and histopathological analysis. The O. sambaquiensis extract, at 0.1 µg/mL, facilitated the neurogenic contractions of the noradrenergic-rich epididymal portion, while reducing the noradrenaline (NA) potency, which suggests an interaction with postsynaptic α1-adrenoceptors. On the other hand, a higher concentration (1 µg/mL) leads to time- and frequency-dependent blockade of nerve-evoked contractions without significantly changing the response to exogenous NA. In turn, the C. quadrumanus extract at 0.1 µg/mL induced blockade of nerve-evoked noradrenergic contractions while reducing the potency to exogenous NA. Both extracts did not affect the purinergic neurotransmission or induce muscle damages. Our results demonstrate that O. sambaquiensis and C. quadrumanus extracts significantly interfere with the noradrenergic neurotransmission without altering purinergic response or smooth muscle structure on rat vas deferens. Such results bring to light the pharmacological potential of O. sambaquiensis and C. quadrumanus molecules for therapeutics focusing on noradrenergic neurotransmission.

Natural Plant Compounds: Does Caffeine, Dipotassium Glycyrrhizinate, Curcumin, and Euphol Play Roles as Antitumoral Compounds in Glioblastoma Cell Lines?

Many plant-derived compounds are shown to be promising antitumor therapeutic agents by enhancing apoptosis-related pathways and cell cycle impairment in tumor cells, including glioblastoma (GBM) cell lines. We aimed to review four natural plant compounds effective in GBM cell lines as caffeine, dipotassium glycyrrhizinate (DPG), curcumin, and euphol. Furthermore, antitumoral effect of these plant compounds on GBM cell lines through microRNAs (miRs) modulation was investigated. However, only DPG and curcumin were found as effective on miR modulation. Caffeine arrests GBM cell cycle in G0/G1 phase by cyclin-dependent kinases (CDK) complex inhibition and by decreasing BCL-2 and increasing FOXO1 expression levels causing greater apoptotic activity. Caffeine can also directly inhibit IP3R3, p38 phosphorylation, and rho-associated protein kinase (ROCK), decreasing cell invasion and migration capacity or indirectly by inhibiting the tissue inhibitor metalloproteinase-1 (TIMP-1) and integrins ß1 and ß3, leading to lower matrix metalloproteinases, MMP-2 and MMP-9. DPG presents antitumoral effect in GBM cells related to nuclear factor kappa B (NF-κB) pathway suppression by IRAK2 and TRAF6-mediating miR-16 and miR-146a, respectively. More recently, it was observed that DPG upregulated miR-4443 and miR-3620, responsible for post-transcriptional inhibition of the NF-κB pathway by CD209 and TNC modulation, respectively leading to lower MMP-9 and migration capacity. Curcumin is able to increase miR-223-3p, miR-133a-3p, miR-181a-5p, miR-34a-5p, miR-30c-5p, and miR-1290 expression leading to serine or threonine kinase (AKT) pathway impairment and also it decreases miR-27a-5p, miR-221-3p, miR-21-5p, miR-125b-5p, and miR-151-3p expression causing p53-BCL2 pathway inhibition and consequently, cellular apoptosis. Interestingly, lower expression of miR-27a by curcumin action enhanced the C/EBP homologous protein(CHOP) expression, leading to paraptosis. Curcumin can inhibit miR-21 expression and consequently activate apoptosis through caspase 3 and death receptor (DR) 4 and 5 activation. Autophagy is controlled by the LC-3 protein that interacts with Atg family for the LC3-II formation and autophagy activation. Euphol can enhance LC3-II levels directly in GBM cells or inhibits tumor invasion and migration through PDK1 modulation.

Effects of dipotassium glycyrrhizinate on wound healing

ABSTRACT Purpose: Dipotassium glycyrrhizinate (DPG) has anti-inflammatory properties, besides promoting the regeneration of skeletal muscle. However, it has not been reported on skin wound healing/regeneration. This research aimed to characterize the effects of DPG in the treatment of excisional wounds by second intention. Methods: Male adults (n=10) and elderly (n=10) Wistar rats were used. Two circular wounds were excised on the dorsal skin. The excised normal skins were considered adult (GAN) and elderly (GIN) naïve. For seven days, 2% DPG was applied on the proximal excision: treated adult (GADPG) and elderly (GIDPG), whereas distal excisions were untreated adult (GANT) and elderly (GINT). Wound healing areas were daily measured and removed for morphological analyses after the 14th and the 21st postoperative day. Slides were stained with hematoxylin-eosin, Masson's trichrome, and picrosirius red. Results: Histological analysis revealed intact (GAN/GIN) and regenerated(GANT/GINT/GADPG/GIDPG) skins. No differences of wounds' size were found among treated groups. Epidermis was thicker after 14 days and thinner after 21 days of DPG administration. Higher collagen I density was found in GIDPG (14th day) and GADPG (21st day). Conclusions: DPG induced woundhealing/skin regeneration, with collagen I, being more effective in the first 14 days after injury.

Neurotoxicity of Olindias sambaquiensis and Chiropsalmus quadrumanus extracts in sympathetic nervous system

Cnidarians are equipped with nematocysts, which are specialized organelles used to inoculate venom during prey capturing and defense. Their venoms are rich in toxins and a potential source of bioactive compounds, however, poorly explored so far. In this work, the activity of the methanolic extracts from the hydromedusa Olindias sambaquiensis and the cubozoan jellyfish Chiropsalmus quadrumanus were studied in sympathetic neurotransmission. For that, bisected rat vas deferens - a classic model of sympathetic neurotransmission - were incubated with the extracts for further myographic and histopathological analysis. The O. sambaquiensis extract, at 0.1 μg/mL, facilitated the neurogenic contractions of the noradrenergic-rich epididymal portion, while reducing the noradrenaline (NA) potency, which suggests an interaction with postsynaptic α1-adrenoceptors. On the other hand, a higher concentration (1 μg/mL) leads to time- and frequency-dependent blockade of nerve-evoked contractions without significantly changing the response to exogenous NA. In turn, the C. quadrumanus extract at 0.1 μg/mL induced blockade of nerve-evoked noradrenergic contractions while reducing the potency to exogenous NA. Both extracts did not affect the purinergic neurotransmission or induce muscle damages. Our results demonstrate that O. sambaquiensis and C. quadrumanus extracts significantly interfere with the noradrenergic neurotransmission without altering purinergic response or smooth muscle structure on rat vas deferens. Such results bring to light the pharmacological potential of O. sambaquiensis and C. quadrumanus molecules for therapeutics focusing on noradrenergic neurotransmission.

Padrão de consumo de alimentos, excesso de peso e risco cardiovascular: uma análise transversal do Estudo Pró-Saúde, 2013 / Patrón de consumo de alimentos, sobrepeso y riesgo cardiovascular: un análisis transversal del Estudio Pro-Salud, Brasil, 2013 / Food consumption patterns, overweight and cardiovascular risk: a cross-sectional analysis of the Pró-Saúde Study, Brazil, 2013

Objetivo: Identificar o padrão de consumo e a associação entre excesso de peso e risco de doença cardiovascular. Métodos: Estudo transversal, com servidores da Universidade do Estado do Rio de Janeiro, Brasil, participantes do Estudo Pró-Saúde. O consumo alimentar foi investigado mediante questionário de frequência alimentar. A associação entre padrões alimentares (exposição), excesso de peso e risco cardiovascular (desfechos) foi estimada por regressão linear. Resultados: Entre 520 avaliados, foram observados quatro padrões alimentares: 'ultraprocessados'; 'saudável'; 'carnes'; 'tradicional'. Nas análises ajustadas, 'carnes' foi inversamente associado à circunferência de cintura (ß=-1,52 - IC95% -2.66;-0,39), índice de massa corporal (IMC) (ß=-0,56 - IC95% -1,01;-0,11) e escore de risco de Framingham (ß=-0,36 - IC95% -0,64;-0,09). Conclusão: Diante do excesso de peso, risco de doenças cardiovasculares e associação inversa entre o padrão alimentar 'carnes' e o IMC, tornam-se importantes novas investigações em populações não trabalhadoras, visando melhor compreender o processo saúde-doença relacionado ao consumo alimentar.

Objetivo: Identificar patrones de consumo y asociación con sobrepeso y riesgo de enfermedad cardiovascular. Métodos: Estudio transversal, con funcionarios de la Universidad del Estado de Rio de Janeiro, Brasil, participantes del Estudio Pro-Salud. Se investigó el consumo de alimentos mediante cuestionario de frecuencia alimentaria. La asociación entre patrones dietéticos (exposición), sobrepeso y riesgo cardiovascular (resultados) se estimó mediante regresión lineal. Resultados: Fueron observados cuatro patrones dietéticos: `ultraprocesado´, `saludable´, `carnes`, `tradicional´. Después del ajuste, el patrón de carne se asoció inversamente con la circunferencia de la cintura (ß=-1,52 - IC95% -2,66 ;-0,386), el índice de masa corporal (ß=-0,56 - IC95% -1,008; -0,108) y el puntaje de riesgo de Framingham (ß=-0,36 - IC95% -0,64;-0,092). Conclusión: En vista del sobrepeso, el riesgo de enfermedades cardiovasculares y la asociación inversa entre el patrón de carne y el IMC, es importante investigar más, en grupos no laborales, con el objetivo de comprender el proceso salud-enfermedad relacionado al consumo de alimentos.

Objective: To identify food consumption patterns and association between overweight and risk of cardiovascular disease. Methods: This was a cross-sectional study with staff of the Universidade do Estado do Rio de Janeiro, Brazil, who took part in the Pró-Saúde Study. Food consumption was investigated using a food frequency questionnaire. Association between dietary patterns (exposure) and overweight and cardiovascular risk (outcomes) was estimated using linear regression. Results: Among the 520 staff assessed, four dietary patterns were found: 'ultra-processed', 'healthy', 'meat' and 'traditional'. After adjustment, the 'meat' pattern was inversely associated with waist circumference (ß=-1.52 - 95%CI -2.66;-0.39), body mass index (ß=-0.56 - 95%CI -1.01;-0.11), and the Framingham Risk Score (ß=-0.36 - 95%CI -0.64;-0.09). Conclusion: In view of excess weight, risk of cardiovascular disease and inverse association between the 'meat' food consumption pattern and BMI, it is important to conduct further investigations, with non-working groups, with the aim of gaining greater understanding of the health-disease process related to food consumption.