Chalcones, a class of natural compounds, characterized by having an α, β-unsaturated carbonyl linking two aromatic rings in their structure, are compounds of great biological relevance and wide variety of biological activities, being important research objects, which is why their obtainment synthetically have great relevance, being a more promising alternative than natural extractivism. Thus, this work aimed at the synthesis and structural elucidation of isoliquiritigenin, (2E)-1-(2,4-dihydroxyphenyl)-3-(4-hydroxyphenyl) prop-2-en-1-one, using aldol condensation Claisen-Schmidt type in basic medium (KOH) of the acylated resorcin (1-(2,4-dihydroxyphenyl) ethan-1-one) with p-hydroxyaldehyde, being possible its identification by means of ¹H and ¹³C NMR spectra.

(1) Background: Osteonecrosis is a rare disease, characterized by the death of bone components and that has as a primary characteristic the considerable reduction in the quality of life of the affected patient, usually young adults. In this context, the purpose of this study is a literature review to evaluate natural products as adjuvants in the treatment of osteonecrosis, their efficacy and main results;

(2) Methods: A search was made in three bibliographic platforms, and the works that addressed the efficacy of natural products as adjuvants in the treatment of osteonecrosis were selected;

(3) Results: Three main natural products showed results of great impact, ratifying the need for further studies on the subject;

(4) Conclusion: The use of natural products presented itself as a promising alternative to be employed as adjuvant to the treatment of osteonecrosis. Therefore, the need for further studies is identified, with the purpose of other natural products that play similar and/or superior roles to those currently known regarding the treatment of osteonecrosis and its adjuvants.

The World Health Organization has been warning about the obesity epidemic affecting different age and socioeconomic groups. Studies have shown the prevalence of diseases associated with obesity, such as gastroesophageal reflux disease (GERD). GERD is a chronic condition resulting from the reflux of stomach contents, which causes tissue damage and symptoms such as heartburn and acid regurgitation. Due to tissue damage and local inflammation, defense cells are present in this process, as they indicate an inflammatory process. An example is the presence of neutrophils at the site, characterized by the activity of the enzyme myeloperoxidase (MPO). Currently, the pharmacological therapy used is proton pump inhibitors (PPIs), such as lansoprazole (LZ), which acts by binding to H+/ATPase enzymes and inhibiting the release of H+ into the gastric lumen. Most of the time, PPIs are effective, but their long-term treatment can have a variety of side effects. New therapeutic targets, such as products from medicinal plant sources, end up being much sought after, due to their greater availability and better efficacy. Among them, there is citral (CT), a monoterpene that is present in the composition of essential oils from plants, such as lemongrass. This monoterpene has several proven pharmacological properties: anti-inflammatory, anti-diabetic, anti-adipogenic and gastroprotective action in the treatment of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). However, there are no data in the literature that demonstrate the action of CT in combating GERD, in in vivo and in vitro studies. Therefore, this project aimed to evaluate the effect of CT on GERD in eutrophic and obese animals. Male mice (C57BL/J6) received standard diet (SD) or high-fat diet (HFD) for 18 weeks to induce obesity (CEUA n°7707010620). To perform the acute treatment, the animals were divided into groups: Tween 80 to 1% – Vehicle; Lz – Lansoprazole; CT25 - Citral 25 mg/kg; CT100 - Citral 100 mg/kg; CT300 - Citral 300 mg/kg; Sham – animals subjected to surgical stress and without treatment. The mice were orally treated by gavage (single dose) and, after one hour, underwent the surgical procedure for implantation of gastroesophageal reflux, being euthanized after four hours to collect the esophagus. Body weight gain, adiposity index, food intake, glycemic index, lesion area, measurement of esophageal pH and evaluations of the inflammatory process via determination of MPO activity were analyzed. Results were expressed as mean ± S.E.M. and statistical significance was determined by Student's t-test and one-way or two-way ANOVA followed by Tukey's test (p<0.05). During the obesity induction period, the animals in the HFD group showed a significant increase in body weight (16%) and in the adiposity index (68%), when compared to the SD group. The results demonstrate that previous treatment with CT in both animals that received SD and HFD (at doses of 25 and 300 mg/kg) was effective in preventing gastroesophageal reflux-induced lesions, in relation to the vehicle group. The results also showed that in the SD group, there was a decrease in the esophageal pH of the animals that received the dose of 100 mg/kg of CT, when compared to the Sham group (CT 100 vs Sham, 4.7 ± 015 vs. 5.6 ± 0.21). Regarding the HFD group, the animals treated with LZ and with CT, at a dose of 300 mg/kg, showed a significant difference when compared to the vehicle and Sham groups (CT 300 vs. Vehicle, 5.8 ± 0.12 vs. 5.1 ± 0.22; CT 300 vs. Sham, 5.8 ± 0.12 vs. 4.8 ± 0.16; LZ vs. Vehicle, 5.8 ± 0.12 vs. 5.1 ± 0.22; LZ vs. Sham, 5.8 ± vs. 4.8 ± 0.12). The MPO enzyme activity was quantified and there was a significant reduction in the group treated with the dose of 300 mg/kg, when compared to the vehicle group in the SD group (CT 300 vs. Vehicle, 4.1 ± 0.72 vs. 12.1 ± 2.27). In the HFD group, this reduction in MPO activity was evident in the LZ, CT100 and CT300 groups, when compared to their vehicle group (LZ vs. Vehicle, 5.3 ± 0.67 vs. 13.1 ± 0.67; CT 100 vs. Vehicle, 5.3 ± 0.82 vs. 13.1 ± 0.67; CT 300 vs. Vehicle, 4.7 ± 1.53 vs. 13.1 ± 0.67). Thus, it was observed that CT had a protective effect on GERD in groups treated with a higher dose of CT in eutrophic and obese animals. Based on the literature and the results obtained, CT is a potential therapeutic target for several diseases, such as that of the gastrointestinal tract, including GERD.

Obesity is a metabolic disorder characterized by the accumulation of fat in the body that poses a risk to the individual's health. This accumulation leads to the development of a low-grade chronic inflammatory process and has been associated with diseases such as type 2 diabetes mellitus, cardiovascular diseases and neurodegenerative diseases. In adipose tissue, changes occur in the profile of immune cells and in the production of adipokines that can compromise insulin sensitivity. In addition to this characteristic inflammatory process in obesity, there are also changes in the lipid profile caused by dyslipidemia in obese animals. The relationship between obesity and metabolic diseases makes the inflammatory pathways an important therapeutic target for study. Many natural products are used in folk medicine for weight loss and have inevitably become interesting therapeutic targets. The medicinal species Baccharis trimera Less (DC), known as carqueja, is used by the population for weight loss and some studies point to a possible anti-obesogenic effect. The aim was to evaluate the effect of Baccharis trimera essential oil (EOBT) in obese mice of the C57BL/6J lineage that consumed a high-fat diet. We split the work on three parts. In the fist part, Male C57BL/J6 mice were subjected to obesity induction through the ingestion of a high-fat diet (60%) for 12 weeks and were orally treated with EOBT at doses of 1, 10 or 100 mg/kg for 14 days. In this study, body mass, food intake, adiposity index, organ weight (liver, kidney, spleen and heart) and the mass of the three adipose tissues (epididymal, retroperitoneal and visceral) were evaluated. All experiments were approved by the Animal Use Ethics Committee (CEUA) of the Institute of Biosciences, UNESP – Campus de Botucatu under protocol number 1156. Parametric data were submitted to the unpaired Student's t test for comparison between two groups and one-way ANOVA for comparison between three groups or more, followed by Tukey's test. For analysis of results with more than one variable, two-way ANOVA was used, followed by the Bonferroni or Tukey test. The minimum value of statistical significance considered was p < 0.05. As a result, it was observed that after 12 weeks with the high-fat diet, the mice showed changes in body mass, adiposity index, and dyslipidemia, other results related to insulin resistance and changes in anti-inflammatory mediators were discussed in other parts. The results indicate that the C57BL/6J mouse strain was able to develop morphological changes and induce dyslipidemia with dietary intake.

Obesity is one of the biggest public health problems in the world, the WHO estimates that more than 700 million adults will be obese by 2025. Obesity is characterized by an excessive accumulation of fat that can compromise health. Adipose tissue (AT) is directly involved in the initiation and maintenance of the inflammatory response triggered by obesity. This metabolic inflammation is responsible for the development of diseases such as type 2 diabetes, cardiovascular diseases and non-alcoholic fatty liver disease. Finding an adequate treatment for obesity and its consequences has proved to be a great challenge. Previous studies have demonstrated the anti-inflammatory and anti-adipogenic potential of Citral, a monoterpene found in plants such as lemon grass and ginger. Citral is an excellent candidate as a therapeutic agent to combat obesity and metabolic inflammation. The aim of this study was to evaluate the curative effect of citral on pro-inflammatory mediators related to obesity-induced hypercaloric diet (HFD) in experimental animals. Male C57BL/6J mice were subjected to HFD (60% of calories from lipids) for 12 weeks then received Citral treatments orally by gavage (25, 100 and 300 mg/kg) for ten, 17 and 24 days. To assess the onset of obesity an oral glucose tolerance test and an insulin tolerance test were performed before and after treatments. At the end of each treatment period, adipose tissue stores were collected for quantification of inflammatory mediators by colorimetric assays. Concomitantly, a group fed with HFD and standard diet (SD, 15% of calories from lipids) treated with vehicle (Tween 80 at 1%, 10 mL/kg) were used as negative and positive controls, respectively. All animal handling and experimental protocols were previously approved by the local ethics committee (protocol nº CEUA 1115). Data are presented as mean ± standard error of the mean, one-way ANOVA with Tukey’s post-hoc test and Student’s t test were used (p<0.05). All animals fed with HFD showed high fasting basal glycemia when compared to control animals. All animals treated with Citral (25, 100 and 300 mg/kg) for ten days presented high levels of IL-4 (p<0.05), IL-5 (p<0.05) and IL-17 (p<0.01) when compared to SD-fed animals. After 17 days of treatment, Citral 100 mg/kg decreased TNF-α (p<0.05) and IL-6 (p<0.01) levels in relation to the vehicle group and IL-1β levels in the Citral group reduced to the level of the SD-fed control group (p>0.05). In addition, Citral (100 mg/kg, 17-day treatment) was able to increase the concentrations of IL-4 and IL-17 (p<0.05) when compared to animals fed with SD. Citral was able to decrease blood glucose without changing insulin sensitivity. A significant decrease in pro-inflammatory mediators and an increase in anti-inflammatory cytokine levels was observed in HFD animals, indicating an action of this monoterpene in combating metabolic inflammation.

The high rate of obesity is a problem that affects people in Brazil and throughout the world. Obesity is linked to an inflammatory process in the different tissues of the body, including hypothalamic regions that are crucial for energy homeostasis. Therefore, a search for a therapy that modulates the neural machinery is an interesting strategy for the treatment of obesity. An important potential therapeutic alternative is citral, a monoterpene which is the major component of essential oils, like lemon grass (Cymbopogon citratus) and ginger (Zingiber officinale), with anti-inflammatory, antioxidant and other activities. Thus, the aim of the present study was to evaluate the effect of citral on hypothalamic inflammation triggered by obesity in male Swiss mice, and to determine the effect of citral on the concentration of pro-inflammatory mediators in the tissue. For this, obesity was induced in Swiss mice (n=10) for 12 weeks on a high-fat diet (60% calories from fat). Citral treatment was administered orally in mice at doses of 25, 100 and 300 mg/kg for seven, 14 and 21 consecutive days. Hypothalamus samples were used to determine cytokines IL-1β, TNF-α, IL-6 through Luminex multiplex assays. The quantified data are presented as the mean ± S.E.M. Parametric data was calculated using Student´s t-test and one way ANOVA followed by Bonferroni test, the results were considered statistically significant at p< 0,05. All experiments were approved by Animal Ethics Committee (AECs), Institute of Biosciences - UNESP, Botucatu under protocol nº 1115.Citral was not able to reduce the body weight of obese mice in the different treatments. Our results shown that hypothalamic inflammation was not installed in the Swiss mice, and it is not possible to analyze an action of the citral on the pro-inflammatory cytokines. In the literature, there are different studies that report the anti-inflammatory action of citral, as well as its action on the body weight of obese mice, however other experimental protocols have been used. C57BL/6J mice have a better profile in the investigation of indicative parameters of diet-induced obesity. Thus, an analysis of the action of citral on hypothalamic inflammation and evolution of body weight in other strain, like C57BL/6J mice is relevant.

The pandemic of new coronavirus pneumonia (COVID-19) is of great concern worldwide, due to the millions of deaths caused in the last year. COVID-19 is characterized by hemodynamic changes, such as venous thromboembolism and intravascular coagulation. In addition to a large release of inflammatory mediators, such as chemoattractant monocyte protein (MCP)-1, inflammatory macrophage protein 1-α (MIP1α), interferon gamma-inducible protein (IP)-10, that inducing a systemic inflammation response (SI). Thus, an important experimental model of SI is the peripheral injection of lipopolysaccharide (LPS) in rodents, which promote the production and release of peripheral inflammatory mediators [tumor necroses factor (TNF)-α, interleukin (IL)-5, IL-10 and fractalkine]. This inflammatory signaling promotes essential survival effector responses, such as an increase in deep body temperature (Tb), also known as fever. The search for new drugs that alleviate this condition can alleviate in SI treatment, mainly, during COVID-19. Myrcene (MCN) is a monoterpene present in the Citrus aurantium essential oil, and their healing, anti-ulcer, anti-inflammatory, antioxidant, and analgesic actions are described in the literature. However, the effect of this monoterpene during SI is unknown. Aim: To evaluate the effect of MCN in euthermic rats against systemic inflammation induced by low-dose LPS. Material and Methods: Male Wistar rats (5-6 weeks, 230-280g, n= 7-8) were used to assess Tb by dataloggers implanted in the abdominal cavity. The rats were orally treated with vehicle - Tween 80-1% (Tw; 10 mL/kg) or MCN (7.5 mg/kg) 30 min before the i.p. administration of induction with LPS (100 µg/kg) or Saline (1 mL/kg). After 360 min of LPS injection, the rats were sacrificed to collected of serum to evaluate the inflammatory mediators’ levels (MIP-1α, MCP-1, IP-10, TNF-α, Fractalkine, IL-10 and IL-5) through Multiplex (Merck Milliplex; Millipore Corporation, Billerica, MA, USA) assay. Statistical significance was determinate by ANOVA followed Tukey post-hoc test (p < 0.05) (CEUA-IBB/UNESP nº 8259150621). Results and Discussion: Rats in the Tw+LPS group present a significant increase in Tb when compared to the control group (Tw+Saline) (Tw+Saline - 53.42 ± 5.42 ºC x min vs. Tw+LPS - 197.4 ± 12.6 ºC x min.). However, the MCN treatment was able to significantly reduce Tb when compared with the Tw+LPS group (Tw+LPS - 197.4 ± 12.6 ºC x min vs. MCN+LPS - 137.1 ± 15.6 ºC x min.), indicating an antipyretic effect of MCN during SI. When investigating the inflammatory signaling caused by LPS administration, the Tw+LPS group showed a significant increase in serum levels of MIP-1α, MCP-1, IP-10, TNF-α, Fractalkine, IL-10, and IL-5, when compared to the control group (p < 0.05). These factors are directly related to thrombosis events and indicators of the systemic inflammatory response during COVID-19. However, our treatment with MCN did not act in the modulation of peripheral signaling to reduce the serum levels of inflammatory mediators, when compared with the Tw+LPS group (p > 0.05). Conclusion: Our data demonstrate that MCN has an antipyretic effect after 360 min LPS administration. However, MCN was not able to reduce inflammatory signaling during SI. Possibly, the monoterpene effect may be involved in central nervous system mechanisms during the inflammatory response caused by LPS injection.

Background: In Brazil, 57.7% of the adult population is overweight and 19.8% is obese. Obesity causes a low-grade inflammatory condition that can result in other comorbidities such as type 2 diabetes mellitus, hypertension, hepatic steatosis and atherosclerosis. In addition, in cases of gastrointestinal tract disorders, there is an increase in the severity of gastric lesions and greater difficulty in the healing process, intensified by the use of medications that further aggravate gastric mucosal lesions in obese individuals. Thus, the literature has reported that obesity delays processes such as the healing of gastric lesions and metalloproteinases are intimately related to this difference. These enzymes play a crucial role in ulcer healing, in the initial phase, the role of MMP-9 is highlighted, and in the later phase, MMP-2. Studies conducted by our group showed that Citral is able to promote healing acceleration through the modulation of inflammatory mediators in ulcers induced by acetic acid in rats, but its healing action associated with obesity condition is still unknown.

Aim: Evaluate the pharmacological effects of Citral on healing process of gastric lesions in eutrophic and obese mice

Material and methods: For induction of obesity, C57Bl-J6 male mice were divided into 2 groups: Standard diet (SD) and high-fat diet (HFD), with 60% of calories from lipids and after 12 weeks of dietary intake, the animals underwent gastric ulcer induction surgery by acetic acid. For injury induction, the animals were anesthetized with isoflurane via inhalation, then they were laparatomized, stomachs exposed to 80% acetic acid application for 20 seconds. For evaluation of the action of Citral, three doses were orally administrated: 25, 100 or 300 mg/kg for 10 subsequent days and the following groups were included: negative control treated with vehicle (Tween 80 at 1%, 10 mL/kg) and positive control treated with Lansoprazole (30 mg/kg). All protocols were approved by the animal use ethics committee of the Institute under the number 1208. All stomachs were collected for macroscopic morphological and zymographic analysis. The macroscopic analysis of the lesions was performed by quantifying the area of regeneration tissue and the ulcer in mm². In addition, we quantified matrix metalloproteinases 2 and 9 by zymography. For statistical analysis, two-way analysis of variance was used, followed by the Tukey or Dunnett test. The minimum significance level adopted for this study was p < 0.05.

Results and discussion: In the group of animals fed with SD, we observed that 10 days after the induction of gastric injury by acetic acid, the treatment of animals with 3 doses of citral did not promote macroscopic changes in gastric lesions compared to the negative control group. There was no difference between the groups in the MMP-2 activity either. However, in animals fed with HFD, there was a significant increase in MMP-9 activity in its intermediate (50%, p < 0.05) and active (13%, p < 0.05) forms in animals treated with the dose of 100 mg/kg of Citral compared to the group treated with vehicle. Since MMP-9 is an enzyme that operates in the early phase of ulcer healing and there was no difference between the areas of lesion, the reduction of its activity may indicate that healing process in the group that received the intermediate dose of Citral was in a more advanced stage of healing.

Conclusion: Although we did not detect macroscopic changes, we found that in obese animals, treatment for 10 days with Citral at a dose of 100 mg/kg reduced MMP-9 activity, indicating that the healing process may be accelerated in this group.

During the last few years, we have learned a lot about diabetes, especially with the passage of time and biotechnological advances, we have seen that not only exist type I or type II diabetes exist, but it is made up of many more types. In the current study, information has been collected from different types of patients and it was deduced that the results in type II diabetes could be improved by identifying what type of treatment should be given to each patient so that they obtain the greatest benefit from the control treatment personalized glycemic from the machine learning model.
The key feature was to identify an improvement and maintenance of glycosylated hemoglobin (HbA1c) in patients below 7% using machine learning when analysing data from combination therapy clinical trials. The trials were focused on phase 3, randomized, double-blind, parallel-group studies treated with a combination of empagliflozin and linagliptin against patients receiving metformin alone. The evaluation of the treatments of the two patient groups was written in detail by the descriptive analysis of the univariate associations between the HbA1c target categories and each baseline characteristic. Upon finalizing the results of the descriptive analysis, machine learning tools such as the classification tree and random forest methods were used to estimate and predict target categories based on patient characteristics.
Maintaining the HbA1c study target protein was shown to be associated with lower baseline HbA1c protein and fasting plasma glucose. With the learning method we saw that the strongest indicators to achieve glycemic maintenance are achieved precisely with the HbA1c protein and fasting plasma glucose. In the experiment, it was other covariates such as body weight, waist circumference, and blood pressure that did not contribute to the final result of the study.

With this study, it could be concluded that using a new machine learning model we could introduce new analysis models to be able to process a large amount of traditional data and be able to extract information such as that of the strongest preacher of the achievement of glycemic control. And above all, these predictions made by the new analyzes could make it easier for us to make clinical decisions in order to have a more effective and personalized treatment for each patient according to their disease status.

Infection by the Helicobacter Pylori microorganism is one of the most common causes of infection, with half of the cases being almost undetectable due to being asymptomatic. This microorganism is responsible for the development of gastric cancer in addition to other metabolic disorders and changes. The problem lies in the fact that in addition to the existence of asymptomatic patients, the conventional methods that currently exist can give false negatives for H. Pylori infection, which can aggravate cases of gastric cancer or even death.
As a result, a different approach to the diagnosis of H. pylori infection has been sought with the artificial intelligence of machine learning and an attempt is made to find a prediction of infection by visual inspection of the gastric mucosa. However, there is no established method of optical diagnosis of H. pylori infection using endoscopic imaging. In this study the objective was to find and demonstrate a reliable precision in the detection by images in the detection of the microorganism.
For the use of information for the study, two independent evaluators carried out independent searches in the most important databases and inclusion data were used where the most notable were endoscopic images without H. pylori infection as a control group and others with images of endoscopy with H. Pylori infection as a group of cases. Disagreements between evaluators were resolved by consulting a third evaluator. Subsequently, a precision meta-analysis of the diagnostic test of 8 studies was performed using criteria such as pooled sensitivity, specificity, diagnostic odds ratio, and area under the AI curve for the detection of H. pylori infection. The use of the AI algorithm reached a total of 82% for the discrimination between infected images against uninfected images.
With this, it can be concluded that the use of algorithms with artificial intelligence as in a field of medicine in the detection of infection of pathogenic organisms is super effective, even being able to give reliable results more quickly.