Botanical Extracts and Compounds of Castanea Plants and Methods of Use: US20190125818A1 - The United States Patent Evaluation.

BACKGROUND: Bacterial infections are increasingly difficult to combat, which makes them a threat to public health on a global level. Staphylococcus aureus is considered one of the main causes of infections in hospitals, as it has a variety of virulence factors, as well as is able to produce bacterial biofilms, which, consequently, bring numerous damages to public health as a result of increased resistance to conventional antibiotics and a longer hospital stay. Therefore, the use of compounds extracted from medicinal plants is a potential pharmaceutically acceptable target, as they do not have toxicity and the potential to disrupt biofilms produced by Staphylococcus aureus already evidenced, thus revealing their relevance to our study. OBJECTIVE: The objective of this work was to perform a critical analysis of a patent with natural extracts against bacterial biofilms found in the United States Patent and Trademark Office (USPTO) database, to map the possible bioactive compounds that may serve as potential future antimicrobial drugs. METHODS: A technological survey was carried out to verify existing patents using natural extracts with anti-biofilm potential. For this, it was searched with the keywords: Botanical extracts AND biofilms; which were performed in the United States Patent and Trademark Office (USPTO) database. Thus, the selected patent used a non-aqueous extract partitioned and vacuum-contracted, subsequently lyophilized for assays with antimicrobial potential. Because of this, a patent was analyzed regarding its chemistry, and biological activity, followed by a critical analysis of the technology proposed in the invention. RESULTS: When using the keywords Botanical extracts AND biofilms in the USPTO, it was possible to find twenty-two inventions; however, only four patents in the USPTO were in agreement with the proposal of the natural extract having antimicrobial activity and an anti-biofilm potential, of which two belonged to the same applicant with similar proposals. The key point of this invention was to enable the compounds of the Castanea sativa plant and its methods of obtaining the extract to present a significant antimicrobial action associated or not with antibiotics, promoting the development of new therapies against bacterial infections capable of disrupting biofilms. The invention developed a methodology for extracting Castanea sativa, in which pentacyclic triterpene compounds were found mostly in its leaves. Whereas for the extraction, the crude methanol extracts called extracts 224 from the ground leaves were made by maceration, filtered, combined, concentrated under pressure in rotary evaporators, and lyophilized. After that, they were resuspended in water and partitioned in succession with hexane, ethyl acetate, and butanol. The most active refined partition was the 224C extract with the solvent ethyl acetate, which was subjected to further fractionation using silica column chromatography. Resulting in the most refined extract, which was 224C-F2, capable of acting directly on the quorum sensing of bacteria, mainly Staphylococcus aureus, blocking the translation of RNAIII, including a series of exotoxins. Regarding the antimicrobial capacity against Staphylococcus aureus, it presented Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of 1.56 µg/mL-1 and > 100 µg/mL -1, respectively. CONCLUSION: Given the analyzed patent, it was possible to verify the importance of alternatives to reduce the impact of bacterial biofilms, which causes damage to industries in general and to health. From this, the invention analyzed has a promising proposal with antimicrobial potential focusing on the great impact of bacterial biofilms. Therefore, natural extracts with antibiofilmic potential can help to minimize the economic losses caused to health due to these multidrug-resistant microorganisms with different virulence mechanisms.

A rare case of mucoepidermoid carcinoma ex-pleomorphic adenoma of the hard palate.

Carcinoma Ex-Pleomorphic Adenoma (CExPA) is a salivary gland carcinoma derived from a primary or recurrent benign pleomorphic adenoma (PA) extremely rare in minor salivary glands. In this paper, we report the case of a male afrodescendant patient, 37 years old, presenting a palatal irregular nodular lesion with approximately 3.5 cm diameter. The lesion had over two years of evolution, but started growing faster and presenting pain and ulceration in the last two months. The incisional biopsy revealed a typical pleomorphic adenoma with focal areas of nests of epidermoid and mucous cells, as well as microcyst formations, resembling the mucoepidermoid carcinoma (MEC). Immunohistochemical analysis revealed positivity for CK7, CK13, CK 14, p63 and Ki67 (about 30%), whereas α-SMA was restricted to the PA component. The diagnosis was CExPA (MEC-type). A discussion on the histopathological and immunohistochemical criteria for differential diagnosis of CExPA is provided in this work, hoping to contribute to a better knowledge and understanding of this rare malignant tumor. Key words:Salivary gland neoplasms, pleomorphic adenoma, adenocarcinoma, mucoepidermoid carcinoma, pathology, differential diagnosis.

Is cysteamine use effective in the treatment of melasma? A systematic review and meta-analysis.

Melasma is a recurrent hypermelanosis disorder characterized by the appearance of brownish and symmetrical spots on the skin. It affects the quality of life and is resistant to available treatment approaches. Cysteamine has been reported as a promising depigmenting agent for melasma treatment and following formulation enhancement, its use is being reported. This review aimed to evaluate the efficacy of the use of depigmenting formulations containing 5% cysteamine in the treatment of patients with melasma. A systematic search was performed in PubMed, Science Direct, and Scielo databases until December 27, 2021, based on criteria selected by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Statistical analysis was performed with Review Manager 5.4 software. The risk of bias was assessed using the Cochrane Risk of Bias Tool for Randomized Trials. A total of six studies containing 120 melasma patients treated with 5% cysteamine were included in this meta-analysis. The meta-analysis demonstrated that 5% cysteamine is effective for the treatment of patients with melasma (MD 6.26 [95% CI 3.68-8.83], p < 0.0001, I2  = 86%). In this review, through meta-analysis allows concluding that 5% cysteamine is effective in the treatment of melasma and presents a low probability of side or adverse effects.

Hesperetin-Based Hydrogels Protect the Skin against UV Radiation-Induced Damage.

UV radiation can cause damages, such as erythema, skin photoaging, and carcinogenesis. The adoption of protective measures against sun exposure is essential to prevent these damages, and the interest in using natural substances as an alternative for photoprotection is growing. Thus, hesperetin with antioxidant, anti-inflammatory, and anticancer properties is a promising substance to be used with photochemopreventive action and to protect the skin from damage induced by UV radiation. Therefore, the present study aimed to develop a topical formulation based on AAMVPC gel containing hesperetin and evaluate its photoprotective effect on the skin of rats exposed to UVA-UVB radiation. The animals were submitted to the irradiation protocol UVA-UVB, and at the end, erythema, lipid peroxidation, and activity of the antioxidant enzyme catalase and superoxide dismutase were evaluated. Additionally, it evaluated the activity of myeloperoxidase and histological changes. The formulation presented a rheological and spreadability profile suitable for cutaneous application. In vivo results demonstrated that the topical formulation of AAMVPC gel containing hesperetin at a concentration of 10% protected the skin from damage induced by UVA-UVB radiation, with the absence of erythema, lipid lipoperoxidation, and inflammation (low myeloperoxidase activity), and increased catalase and superoxide dismutase activities. The morphology and architecture of the dermo-epidermal tissue of these animals were like those observed under normal conditions (non-irradiated animals). Thus, the results showed that hesperetin was able to protect the animals' skin against UV radiation-induced skin damage and the protection mechanisms may be related to the antioxidant and anti-inflammatory properties of this natural product.

Oral basaloid squamous cell carcinoma: A case report with emphasis on histopathological diagnosis criteria.

Basaloid squamous-cell carcinoma (BSCC) is an uncommon variant of squamous cell carcinoma (SCC) consisting of atypical squamous and basaloid cells. It is an aggressive lesion that most commonly affects the oropharynx, being rare in intraoral sites. In this paper, we report the case of a male patient, 42 years old, smoker and chronic drinker, presenting a vegetating and ulcerated leukoerythroplastic lesion, asymptomatic, with five months of evolution, located on the floor of the mouth. Bilateral infarction of the submandibular lymph nodes was observed. Having established the presumptive diagnosis of SCC, an incisional biopsy was performed, which revealed a proliferation of nests and trabeculae of atypical basaloid and squamous cells. Immunohistochemical analysis revealed positivity for AE1/AE3, CK 5, CK 14, p63 and Ki67 (>80%), but negativity for CK7, S-100 and α-SMA. The diagnosis was BSCC. The patient was referred to a head and neck surgery and oncology service for definitive treatment, but died five months after diagnosis. BSCC is a clinicopathological entity whose diagnosis can be challenging. Its aggressive clinical behavior reiterates the relevance of the correct diagnosis for instituting the appropriate treatment. Thus, it is intended, in this work, to discuss the histopathological criteria for differential diagnosis of BSCC, aiming to contribute to its better knowledge and, perhaps, understanding.