Oral gavage delivery of Cornus officinalis extract delays type 1 diabetes onset and hyperglycemia in non-obese diabetic (NOD) mice.

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences, which result in the specific destruction of insulin-producing pancreatic ß-cells. Currently, there are over 1.6 million cases of T1D in the United States with a worldwide incidence rate that has been increasing since 1990. Here, we examined the effect of Cornus officinalis (CO), a well-known ethnopharmacological agent, on a T1D model of the non-obese diabetic (NOD) mouse. A measured dose of CO extract was delivered into 10-week-old NOD mice by oral gavage for 15 weeks. T1D incidence and hyperglycemia were significantly lower in the CO-treated group as compared to the water gavage (WT) and a no handling or treatment control group (NHT) following treatment. T1D onset per group was 30%, 60% and 86% for the CO, WT and NHT groups, respectively. Circulating C-peptide was higher, and pancreatic insulitis was decreased in non-T1D CO-treated mice. Our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to slow early stage T1D progression.

Treatments for Burning Mouth Syndrome: A Network Meta-analysis.

The aim of this systematic review and network meta-analysis (NMA) of randomized controlled trials was to evaluate the effectiveness of treatments for pain relief of burning mouth syndrome (BMS). Five databases and gray literature were searched. Independent reviewers selected studies, extracted data, and assessed the risk of bias. The primary outcome was pain relief or burning sensation, and the secondary outcomes were side effects, quality of life, salivary flow, and TNF-α and interleukin 6 levels. Four comparable interventions were grouped into different network geometries to ensure the transitivity assumption for pain: photobiomodulation therapy, alpha-lipoic acid, phytotherapics, and anxiolytics/antidepressants. Mean difference (MD) and 95% CI were calculated for continuous outcomes. The minimal important difference to consider a therapy beneficial against placebo was an MD of at least -1 for relief of pain. To interpret the results, the GRADE approach for NMA was used with a minimally contextualized framework and the magnitude of the effect. Forty-four trials were included (24 in the NMA). The anxiolytic (clonazepam) probably reduces the pain of BMS when compared with placebo (MD, -1.88; 95% CI, -2.61 to -1.16; moderate certainty). Photobiomodulation therapy (MD, -1.90; 95% CI, -3.58 to -0.21) and pregabalin (MD, -2.40; 95% CI, -3.49 to -1.32) achieved the minimal important difference of a beneficial effect with low or very low certainty. Among all tested treatments, only clonazepam is likely to reduce the pain of BMS when compared with placebo. The majority of the other treatments had low and very low certainty, mainly due to imprecision, indirectness, and intransitivity. More randomized controlled trials comparing treatments against placebo are encouraged to confirm the evidence and test possible alternative treatments (PROSPERO CRD42021255039).

Proteomic examination of Cornus officinalis stimulated 1.1B4 human pancreatic cells reveals activation of autophagy and Keap1/Nrf2 pathway.

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences culminating in the immunologically mediated destruction of pancreatic ß-cells with eventual loss of insulin production. Although T1D can be accurately predicted via autoantibodies, therapies are lacking that can intercede autoimmunity and protect pancreatic ß-cells. There are no approved interventional modalities established for this purpose. One such potential source for clinical agents of this use is from the frequently utilized Cornus officinalis (CO) in the field of ethnopharmacology. Studies by our lab and others have demonstrated that CO has robust proliferative, metabolic, and cytokine protective effects on pancreatic ß-cells. To identify the molecular mechanism of the biological effects of CO, we performed a proteomic and phosphoproteomic analysis examining the cellular networks impacted by CO application on the 1.1B4 pancreatic ß-cell line. Our label-free mass spectrometry approach has demonstrated significant increased phosphorylation of the selective autophagy receptor of p62 (Sequestosome-1/SQSTM1/p62) and predicted activation of the antioxidant Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid factor 2-related factor 2 (Nrf2) pathway. Further validation by immunoblotting and immunofluorescence revealed markers of autophagy such as increased LC3-II and decreased total p62 along with nuclear localization of Nrf2. Both autophagy and the Keap1/Nrf2 pathways have been shown to be impaired in human and animal models of T1D and may serve as an excellent potential therapeutic target stimulated by CO.

Chemical profile dataset of Cornus officinalis from multiple sources using HPLC/MS.

This article displays raw data linked to the research article "Compositional Analysis and Biological Characterization of Cornus officinalis on Human 1.1B4 Pancreatic ß Cells" [1]. This data was generated by utilizing HPLC/(+and -)ESI-MSn on Cornus officinalis (CO) from four independent sources [1]. The aim was to identify the chemical profile of CO from multiple sources to compare the similarities and differences resulting from various processing methods, and compile a list of known and novel constituents to elucidate the bioactive ingredients. This report contains the full chromatogram and a raw list of the constituents found in CO including chemical name, retention time, and molecular weight from all four sources. All data from HPLC/MS analysis is raw and unprocessed.

Compositional analysis and biological characterization of Cornus officinalis on human 1.1B4 pancreatic ß cells.

Type 1 diabetes (T1D) is an autoimmune disease resulting from the loss of pancreatic ß cells and subsequent insulin production. Novel interventional therapies are urgently needed that can protect existing ß cells from cytokine-induced death and enhance their function before symptomatic onset. Our initial evidence is suggesting that bioactive ingredients within Cornus officinalis (CO) may be able to serve in this function. CO has been extensively used in Traditional Chinese Medicine (TCM) and reported to possess both anti-inflammatory and pro-metabolic effects. We hypothesize that CO treatment may provide a future potential candidate for interventional therapy for early stage T1D prior to significant ß cell loss. Our data demonstrated that CO can inhibit cytokine-mediated ß cell death, increase cell viability and oxidative capacity, and increase expression of NFATC2 (Nuclear Factor of Activated T Cells, Cytoplasmic 2). We have also profiled the bioactive components in CO from multiple sources by HPLC/MS (High Performance Liquid Chromatography/Mass Spectrometry) analysis. Altogether, CO significantly increases the energy metabolism of ß cells while inducing the NFAT pathway to signal for increased proliferation and endocrine function.

Future Prospects of Biologic Therapies for Immunologic Diseases.

This article presents an overview of future uses for biologic therapies in the treatment of immunologic and allergic conditions. Discussion is centered on the use of existing therapies outside of their current indication or on new therapies that are close to approval. This information may help familiarize practicing allergists and immunologists with therapies they may soon encounter in their practice as well as help identify conditions and treatments that will require further study in the near future.

Crescimento, produção de fitomassa e teor de óleo essencial de folhas de capim citronela (Cymbopogon nardus (L. ) Rendle) em cultivo consorciado com algodoeiro colorido no semiárido mineiro / Growth, phytomass yield and essential oil content of leaves of citronella grass [Cymbopogon nardus (L. ) Rendle] intercropping with colored cotton

Avaliou-se o crescimento, a produção e o teor do óleo essencial de dois cortes de capim citronela em cultivo consorciado com algodoeiro colorido no semiárido. Para isso foram utilizados dois sistemas de consórcios (tratamentos): algodão colorido consorciado com capim citronela 3x1 e algodão colorido consorciado com capim citronela 1x1. A variedade de algodão colorido utilizada foi a BRS Rubi e as mudas de capim citronela foram produzidas no Horto de Plantas Medicinais da Unimontes. O delineamento experimental utilizado foi em blocos casualizados com dois tratamentos e 16 repetições. O experimento foi mantido em regime de sequeiro e foi avaliado a altura das plantas de capim citronela. Foram realizadas duas colheitas das folhas de capim citronela, sendo a primeira no momento da colheita da fibra do algodão e a segunda na rebrota do capim, seis meses após. Todas as plantas da parcela foram colhidas e as folhas frescas foram pesadas, no campo, com o auxílio de balança digital. Amostras das folhas colhidas foram retiradas e levadas para secagem em estufa com circulação forçada de ar a 35ºC até atingirem massa constante. Foi verificada a massa seca e posteriormente realizada a extração do óleo essencial pelo método de hidrodestilação em aparelho modificado de Clevenger. Os dados foram submetidos à análise de variância e as médias comparadas pelo teste Skott-Knott (p<0,05). A altura das plantas não diferiu entre os tratamentos nas colheitas. Para a produção de massa fresca e seca houve diferença entre os tratamentos apenas na segunda colheita. Neste caso, as plantas cultivadas em consórcio 1x1 produziram mais do que as do consórcio 3x1. O teor de óleo essencial de capim citronela não variou entre os dois sistemas de consórcio, tanto no primeiro como no segundo corte.

The research was performed to evaluate the growth, production and essential oil content of the two harvests of citronella grass in intercropped with colored cotton in semiarid.For this, was used two system consortium (treatments): colored cotton intercropped with citronella grass 3X1 and colored cotton intercropped with citronella grass 1X1. The variety of colored cotton used was BRS Rubi and the citronella grass seedlings were produced in the Medicinal Plants Garden of Unimontes. The experimental design used was randomized blocks with two treatments and 16 repetitions. The experiment was maintained under rainfed conditions. Was evaluated plant height of citronella grass. Citronella grass leaves were harvested twice: the first was made at harvest of cotton fiber and the second in the grass regrowth, six months later. All plants in the plot were harvested and the fresh leaves were weighed, in the field, with the aid of a digital balance. Samples from leaves harvested were collected and taken for drying in an oven with forced air at 35ºC until reaching constant weight. Dry mass was verified and the performed the extraction of essential oil by hydrodestilation in Clevenger modified apparatus. Data were subjected to analysis of variance and means compared by Skott-Knott test (p<0.05). The plants height did not differ between treatments in harvests. For the production of fresh and dry mass was significant difference between treatments only in the second harvest. In this case the plants cultivated in the consortium 1x1 produced more than in the consortium 3x1. The essential oil content of citronella grass did not vary between the two systems consortium, in the first and the second harvest.

Adaptações fisiológicas e anatômicas de melissa officinalis L. (Lamiaceae) cultivadas sob malhas termorrefletoras em diferentes intensidades luminosas / Physiological and morphological adaptations of melissa officinalis L. (Lamiaceae) cultivated under thermo-reflector shading nets at different luminous intensities

Objetivou-se, com a realização da pesquisa, avaliar modificações fisiológicas e anatômicas em plantas de melissa, cultivadas sob malhas termorrefletoras (Aluminet®), em diferentes níveis de sombreamento, visando conhecer a plasticidade fenotípica em resposta de adaptação a diferentes quantidades de luz. Os tratamentos foram caracterizados por plantas submetidas a pleno sol e a 20 e 60 por cento de intensidade luminosa, e arranjados conforme o delineamento inteiramente casualizado (DIC). As quantificações de clorofila foram feitas em quatro repetições, as medições das epidermes e parênquimas foram repetidas 15 vezes e utilizou-se 10 repetições para as avaliações das características de cloroplastos e grãos de amido destes. Plantas submetidas a 20 por cento de intensidade luminosa apresentaram maior quantidade de clorofila a e, portanto, maior razão clorofila a/b. Comparativamente, as folhas de melissa a pleno sol e a 60 por cento de luz apresentaram células da epiderme adaxial mais espessas, mas as células da epiderme abaxial mostraram características encontradas em folhas de sombra, ou seja, mais finas. Quanto maior a intensidade luminosa, maior o número de cloroplastos, porém, a pleno sol mostraram-se mais finos e com menor área. Os grãos de amido de plantas cultivadas sob ambientes sombreados tiveram maior área e ocuparam maior parte nos cloroplastos de plantas a 60 por cento de intensidade luminosa. Assim, plantas de melissa, quando submetidas ao sombreamento, tiveram plasticidade fenotípica.

The aim of this study was to evaluate physiological and anatomical modifications in lemon balm plants, cultivated under thermo-reflector nets (Aluminet®) at different levels of shading, in order to understand the phenotypic plasticity in adaptation response to different light quantities. The treatments were characterized by plants subjected to full sun and 20 and 60 percent of luminous intensity, and arranged in completely randomized design (CRD). The quantifications of chlorophylls were done in four replicates, the measurements of epidermis and parenchymas were repeated 15 times and 10 replicates were used to evaluate characteristics of chloroplasts and their starch grains. Plants subjected to 20 percent of luminous intensity showed higher quantity of chlorophyll a and, therefore, higher chlorophyll a/b ratio. Lemon balm leaves under full sun and 60 percent of light showed thicker adaxial epidermis cells, but the abaxial epidermis cells showed characteristics found in shaded leaves, i.e., they were slender. The higher the light intensity, the larger the number of chloroplasts; however, under full sun, they were slender and had smaller area. The starch grains of leaves grown under shaded environments showed larger area and, at 60 percent of luminous intensity, occupied the largest part of chloroplasts. Thus, lemon balm plants, subjected to shading conditions, showed phenotypic plasticity.

Adubação orgânica na produção de biomassa de plantas, teor e qualidade de óleo essencial de orégano (Origanum vulgare L. ) em cultivo protegido / Organic fertilization on phytomass production and essential oil content and quality of oregano (Origanum vulgare L. ) under protected cultivation

Origanum vulgare L., conhecida como orégano, é considerada planta condimentar largamente usada na culinária. No Brasil poucas são as pesquisas com esta espécie visando maximização das técnicas de cultivo. Objetivou-se avaliar os efeitos de diferentes doses dos adubos orgânicos bovino e aves no crescimento de plantas, teor de clorofila, teor, rendimento e qualidade do óleo essencial de orégano cultivado sob estufa. Foram conduzidos dois ensaios, sendo um com esterco bovino e o outro com esterco de aves (Poedeira). Plantas de orégano (Origanum vulgare L.) foram cultivadas em vasos de 10 L submetidas aos seguintes tratamentos: Ensaio I: Esterco bovino: 1) Solo sem adubação (controle); 2) solo + 3,0 kg m-2 de esterco bovino; 3) solo + 6,0 kg m-2 de esterco bovino; 4) solo + 9,0 kg m-2 de esterco bovino; 5) solo + 12,0 kg m-2 de esterco bovino; Ensaio II - Esterco de aves: 1) solo sem adubação (Controle); 2) solo + 1,5 kg m-2 de esterco de galinha; 3) solo + 3,0 kg m-2 de esterco de galinha; 4) solo + 4,5 kg m-2 de esterco de galinha e 5) solo + 6,0 kg m-2 de esterco de galinha. Ambos os ensaios foram conduzidos em delineamento blocos ao acaso com 4 repetições e a parcela experimental composta de 4 vasos. Foi observado que as doses de adubos bovino e avícola influenciaram significativamente no crescimento das plantas, rendimento e composição química do óleo essencial de orégano.

Origanum vulgare L., known as oregano or wild marjoram, is an aromatic plant widely used in cookery. In Brazil, there are few studies with this species aimed at improving the cultivation techniques. The present study was carried out to evaluate the effect of different levels of cattle and chicken organic manure on plant growth, chlorophyll content, besides essential oil content, yield and quality of oregano grown in a greenhouse. Two assays were carried out, one of them used cattle manure and the other, chicken manure (Hen). Oregano (Origanum vulgare L.) plants were grown in 10L-pots and subjected to the following treatments: Assay I: Cattle manure: 1) Soil without fertilization (control); 2) Soil + 3.0 kg m-2 cattle manure; 3) Soil + 6.0 kg m-2 cattle manure; 4) Soil + 9.0 kg m-2 cattle manure; and 5) Soil + 12.0 kg m-2 cattle manure; Assay II: Chicken manure: 1) Soil without fertilization (control); 2) Soil + 1.5 kg m-2 chicken manure; 3) Soil + 3.0 kg m-2 chicken manure; 4) Soil + 4.5 kg m-2 chicken manure; and 5) Soil + 6.0 kg m-2 chicken manure. The experimental design for both assays was in randomized blocks with four replicates and four pots per plot. Cattle and chicken manure levels significantly influenced oregano plant growth besides essential oil yield and chemical composition.

Accuracy of detecting changes in auditory heart rate in a simulated operating room environment.

The threshold for the identification of changes in heart rate and the accuracy in estimating heart rate were compared between 20 anaesthetists and 20 non-anaesthetists in a simulated operating theatre, both with and without distraction tasks. Typical operating theatre distractions were simulated by requiring anaesthetists and non-anaesthetists to perform secondary tasks. There were no differences found between the groups in identification of heart rate changes. The distraction tasks reduced performance in both groups (to a greater extent in the anaesthetists group). A change of > 10 beats per minute was required for 80% of the changes to be detected. An upward heart rate change was more easily detected than a reduction. Anaesthetists were found to be marginally better at estimating the heart rate change from an auditory tone alone. However, the study did not confirm that anaesthetists have a superior ability to detect changes in heart rate than non-anaesthetists.

Office-based transurethral microwave thermotherapy using the TherMatrx TMx-2000.

BACKGROUND AND PURPOSE: Transurethral microwave thermotherapy (TUMT) is an effective therapy for symptomatic benign prostatic hyperplasia (BPH), but the trade-off between the magnitude of clinical improvement and side effects and patient tolerance has limited its appeal to patients and urologists. This study, using the TherMatrx TMx-2000, a TUMT device that directly heats the transition zone to greater than 50 degrees C, has been focused on resolving these issues and developing a truly office-based therapy that is well tolerated with a benign post-treatment course. PATIENTS AND METHODS: This study was multi-institutional and designed as a blinded, randomized, and sham-controlled trial. A series of 200 patients with an AUA Symptom Index (AUASI) of >12, a peak flow rate of <12 mL/sec, and cystoscopic evidence of BPH were randomized 2:1 (active to sham) and treated in seven physician offices under a Food and Drug Administration-supervised and audited premarket approval protocol. No intravenous sedation was used in any patient. Follow-up for the sham-treatment group was 3 months, at which time, patients could cross over to an active treatment. A total of 119 patients have completed 1-year follow-up. RESULTS: The active and sham groups were statistically identical at baseline. The 1-hour total treatment was extremely well tolerated using urethral lidocaine and oral medications; not a single prostate block or parental dose of medication was required. The active-treatment group demonstrated a statistically significant reduction (p < 0.05) in AUASI at 3 months compared with sham treatment, with an AUASI decrease from 22.4 to 12.4 (n = 124) for active v 22.9 to 17 for sham (n = 62). For the 119 patients in the active arm who have reached 12 months, the AUASI has fallen to 10.6 points (47.1% decrease), and the peak flow rate has increased 5.0 mL/sec (58.1%). Postprocedure catheterization was typically 2 or 3 days, and the 16.8% of patients who failed their first voiding trial all voided within 1 week. No major adverse events such as stricture, rectal findings, or ejaculatory changes have been reported. CONCLUSIONS: This study demonstrates that the TherMatrx TMx-2000 TUMT effectively treats symptomatic BPH in the physician office with minimal morbidity.

Increased use of cardiovascular medications in seniors prescribed non-ASA non-steroidal anti-inflammatory drugs.

The objective of this study was to determine the relationship between the prescribing of non-ASA non-steroidal anti-inflammatory drugs (NANSAID) and the prescribing of select cardiovascular (CV) medications. We performed a retrospective, cross-sectional analysis of the prescribed use of these medications between December 1, 1990 and June 30, 1991 by Albertans 65 years of age and older utilizing data from the publically-funded drug benefit plan. Variables examined were: the number of individuals prescribed NANSAID and CV medications; mean daily dose for these medications; calculated relative dose; the proportion of NANSAID users prescribed CV medications compared to non-users; and the relative proportions of users of specific NANSAID prescribed CV medication. We found that 33.4% and 19.6% of Albertan seniors were prescribed CV medications and NANSAID, respectively. NANSAID users were twice as likely to be prescribed CV medications as compared to non-users. Intermediate/high dose NANSAID users were more likely to be prescribed a CV medication as compared to low-dose users. The risk of being prescribed a CV medication was highest for indomethacin and users of multiple NANSAID, while ibuprofen users had the lowest risk. We conclude that NANSAID users are more likely to be also prescribed CV medications. Subjects who consume a lower dose of NANSAID are less likely to be prescribed CV medications. For different NANSAID, there is a spectrum of risk.

Comparison of plain with pH-adjusted bupivacaine with hyaluronidase for peribulbar block.

Fifty patients scheduled for cataract surgery under peribulbar block were randomised to receive either plain (pH 5.4) or pH-adjusted (pH 6.8 range 6.7-6.9) 0.75% bupivacaine. Hyaluronidase was added to both solutions prior to peribulbar block. The time of onset of akinesia of the globe and the need for supplementary injections were recorded by an independent observer. Patients who returned for surgery to the second eye received the alternative local anaesthetic solution for the second peribulbar block. The relative efficacy of the different anaesthetic solutions was compared in patients who underwent unilateral surgery (Group A, n = 50). In 12 patients (Group B) who underwent bilateral surgery, direct comparisons between eyes in the same patient were possible. In both groups of patients, eyes receiving peribulbar block with the pH-adjusted solution showed a shorter time to partial akinesia of the globe (P less than 0.05). However, there was no difference between the solutions in the time to complete akinesia of the globe, but the number of supplementary injections required for an effective block with the pH-adjusted solution was increased. Onset time to akinesia of the lateral and superior rectus muscles was shortened in patients receiving the pH-adjusted solution but there were minimal effects on the medial and inferior recti.