Exploring CDKN1A Upregulation Mechanisms: Insights into Cell Cycle Arrest Induced by NC2603 Curcumin Analog in MCF-7 Breast Cancer Cells.

Breast cancer stands out as one of the most prevalent malignancies worldwide, necessitating a nuanced understanding of its molecular underpinnings for effective treatment. Hormone receptors in breast cancer cells substantially influence treatment strategies, dictating therapeutic approaches in clinical settings, serving as a guide for drug development, and aiming to enhance treatment specificity and efficacy. Natural compounds, such as curcumin, offer a diverse array of chemical structures with promising therapeutic potential. Despite curcumin's benefits, challenges like poor solubility and rapid metabolism have spurred the exploration of analogs. Here, we evaluated the efficacy of the curcumin analog NC2603 to induce cell cycle arrest in MCF-7 breast cancer cells and explored its molecular mechanisms. Our findings reveal potent inhibition of cell viability (IC50 = 5.6 µM) and greater specificity than doxorubicin toward MCF-7 vs. non-cancer HaCaT cells. Transcriptome analysis identified 12,055 modulated genes, most notably upregulation of GADD45A and downregulation of ESR1, implicating CDKN1A-mediated regulation of proliferation and cell cycle genes. We hypothesize that the curcumin analog by inducing GADD45A expression and repressing ESR1, triggers the expression of CDKN1A, which in turn downregulates the expression of many important genes of proliferation and the cell cycle. These insights advance our understanding of curcumin analogs' therapeutic potential, highlighting not just their role in treatment, but also the molecular pathways involved in their activity toward breast cancer cells.

Freezing/thawing as an accelerating process of wet- and dry-aged Nellore beef.

This study aimed to evaluate the use of freezing/thawing as a way of accelerating the aging processes of beef from Nellore animals. Non-frozen (NF) or freezing/thawing (FT) strip loins were aged (for 14 and 28 days) using two systems: bone-in dry-aging (DA); boneless wet-aging (WA). FT-treated samples had greater weight losses (P < 0.05) during aging than NF-treated samples, especially using the DA process. However, the weight loss of the FT 14-days DA beef samples was comparable to that of NF 28-days DA. FT beef had lower fragmentation index and shear force values (P < 0.05), as well as its maximum sensorial tenderness was achieved earlier (P < 0.05) than the NF counterpart. With 28 days of aging, DA beef showed higher (P < 0.05) tenderness and juiciness scores and lower lightness values than WA beef. The FT process decreased the reducing capacity of meat samples, generating more metmyoglobin and lower amounts of chroma than NF. The expected volatile profile of DA beef was achieved faster in FT-treated samples, but the freezing treatments did not compromise the microbial count for either aging system. Our findings indicate that accelerated DA by the FT process could improve the palatability of Nellore beef, allowing the desired tenderness and flavor profile to be achieved in a shorter time, without increasing costs with weight losses or adversely affecting physicochemical, chemical, and microbial characteristics.

Clinical characterization, physical frailty, and depression in elderly patients with psoriasis from a reference center in Brazil: a cross-sectional study

Abstract Background: There are few studies dedicated to the characterization of the geriatric population with psoriasis, which has particularities in terms of clinical manifestations and therapeutic limitations. As psoriasis is a chronic disease, presenting a higher prevalence with age, the increase in life expectancy in Brazil demands knowledge about the behavior of the disease among the elderly. Objectives: To characterize elderly people with psoriasis from a tertiary service, from the clinical-epidemiological point of view, presence of comorbidities, physical frailty, and affective impact, and to compare these aspects with adults with psoriasis and elderly people without the disease. Methods: Cross-sectional study of 64 elderly patients with psoriasis, 64 adults with psoriasis, and 64 elderly patients without the disease. Clinical-demographic aspects, the Beck depression scale, and Skindex-16 were evaluated. Indicators of physical frailty were evaluated in elderly patients: handgrip, sit-to-stand test, fatigue, and weight loss >5%. Results: In the elderly, the mean age (SD) of psoriasis onset was 44 (10) years, men represented 47% of the sample, the prevalence of arthritis was 22%, and ungual involvement occurred in 72%. Topical corticosteroids were used more often among elderly people with psoriasis (100%) than among adults with the disease (86%), with no difference among other systemic treatments. Diabetes mellitus occurred in 30% of the elderly. Hypertension (59%), dyslipidemia (52%), depression (34%), and fatigue (59%) were more prevalent among the elderly with psoriasis than among the healthy controls.

Clinical characterization, physical frailty, and depression in elderly patients with psoriasis from a reference center in Brazil: a cross-sectional study.

BACKGROUND: There are few studies dedicated to the characterization of the geriatric population with psoriasis, which has particularities in terms of clinical manifestations and therapeutic limitations. As psoriasis is a chronic disease, presenting a higher prevalence with age, the increase in life expectancy in Brazil demands knowledge about the behavior of the disease among the elderly. OBJECTIVES: To characterize elderly people with psoriasis from a tertiary service, from the clinical-epidemiological point of view, presence of comorbidities, physical frailty, and affective impact, and to compare these aspects with adults with psoriasis and elderly people without the disease. METHODS: Cross-sectional study of 64 elderly patients with psoriasis, 64 adults with psoriasis, and 64 elderly patients without the disease. Clinical-demographic aspects, the Beck depression scale, and Skindex-16 were evaluated. Indicators of physical frailty were evaluated in elderly patients: handgrip, sit-to-stand test, fatigue, and weight loss >5%. RESULTS: In the elderly, the mean age (SD) of psoriasis onset was 44 (10) years, men represented 47% of the sample, the prevalence of arthritis was 22%, and ungual involvement occurred in 72%. Topical corticosteroids were used more often among elderly people with psoriasis (100%) than among adults with the disease (86%), with no difference among other systemic treatments. Diabetes mellitus occurred in 30% of the elderly. Hypertension (59%), dyslipidemia (52%), depression (34%), and fatigue (59%) were more prevalent among the elderly with psoriasis than among the healthy controls. STUDY LIMITATIONS: The study was carried out in a public reference service for patients with psoriasis, all of which were undergoing treatment. CONCLUSIONS: Elderly people with psoriasis from a tertiary service showed greater affective impairment, metabolic comorbidities, and physical frailty than elderly controls.

Merging short and stranded long reads improves transcript assembly.

Long-read RNA sequencing has arisen as a counterpart to short-read sequencing, with the potential to capture full-length isoforms, albeit at the cost of lower depth. Yet this potential is not fully realized due to inherent limitations of current long-read assembly methods and underdeveloped approaches to integrate short-read data. Here, we critically compare the existing methods and develop a new integrative approach to characterize a particularly challenging pool of low-abundance long noncoding RNA (lncRNA) transcripts from short- and long-read sequencing in two distinct cell lines. Our analysis reveals severe limitations in each of the sequencing platforms. For short-read assemblies, coverage declines at transcript termini resulting in ambiguous ends, and uneven low coverage results in segmentation of a single transcript into multiple transcripts. Conversely, long-read sequencing libraries lack depth and strand-of-origin information in cDNA-based methods, culminating in erroneous assembly and quantitation of transcripts. We also discover a cDNA synthesis artifact in long-read datasets that markedly impacts the identity and quantitation of assembled transcripts. Towards remediating these problems, we develop a computational pipeline to "strand" long-read cDNA libraries that rectifies inaccurate mapping and assembly of long-read transcripts. Leveraging the strengths of each platform and our computational stranding, we also present and benchmark a hybrid assembly approach that drastically increases the sensitivity and accuracy of full-length transcript assembly on the correct strand and improves detection of biological features of the transcriptome. When applied to a challenging set of under-annotated and cell-type variable lncRNA, our method resolves the segmentation problem of short-read sequencing and the depth problem of long-read sequencing, resulting in the assembly of coherent transcripts with precise 5' and 3' ends. Our workflow can be applied to existing datasets for superior demarcation of transcript ends and refined isoform structure, which can enable better differential gene expression analyses and molecular manipulations of transcripts.

Genetics of sexually dimorphic adipose distribution in humans.

Obesity-associated morbidity is exacerbated by abdominal obesity, which can be measured as the waist-to-hip ratio adjusted for the body mass index (WHRadjBMI). Here we identify genes associated with obesity and WHRadjBMI and characterize allele-sensitive enhancers that are predicted to regulate WHRadjBMI genes in women. We found that several waist-to-hip ratio-associated variants map within primate-specific Alu retrotransposons harboring a DNA motif associated with adipocyte differentiation. This suggests that a genetic component of adipose distribution in humans may involve co-option of retrotransposons as adipose enhancers. We evaluated the role of the strongest female WHRadjBMI-associated gene, SNX10, in adipose biology. We determined that it is required for human adipocyte differentiation and function and participates in diet-induced adipose expansion in female mice, but not males. Our data identify genes and regulatory mechanisms that underlie female-specific adipose distribution and mediate metabolic dysfunction in women.

Sexually-transmitted monkeypox: report of two cases

Abstract Monkeypox is an emerging infection that has spread to all continents since May 2022. It is caused by the zoonotic monkeypox virus, consisting of double-stranded DNA, belonging to the Orthopoxvirus genus of the Poxviridae family, which has high transmissibility, especially by contact with the skin, favoring its sexual transmission. This case report describes a same-sex male couple, both aged 28 years old, without comorbidities. In the index case, perioral and penile lesions started ten days before the consultation, with rapid progression and a high fever that started eight days after the appearance of the lesions. In the second case, the perioral lesions started three days after the partner; however, he remained afebrile. Both were isolated, treated with symptomatic measures, and, after ulceration, the lesions completely regressed in 14 days. Dermatologists should be aware of manifestations of monkeypox, which may include vesiculopustular lesions in areas of sexual contact, as well as oligosymptomatic cases or cases with few skin lesions.

Pigmented eccrine poroma in an atypical location

Abstract Eccrine poroma is the term that includes benign neoplasms of the terminal duct of the eccrine sweat glands, which may clinically and dermoscopically resemble other melanoma and non-melanoma skin tumors. They are often located on the extremities (especially palms and soles), presenting as normochromic or erythematous papules and nodules, measuring up to 2 cm. Pigmented variants are uncommon, accounting for less than 20% of cases. This report describes a 37-year-old man who developed a large pigmented eccrine poroma on his right shoulder, causing diagnostic difficulty. Histopathological examination revealed a nodular neoplasm consisting of small, monomorphic, cuboidal cells, with ample, eosinophilic cytoplasm and well-defined borders, in addition to conspicuous intercellular bridges, with melanin deposits diffusely distributed inside them. The absence of cytological atypia, cellular pleomorphism, increased mitotic activity, and necrosis foci corroborated the diagnostic exclusion of porocarcinoma, which can develop from eccrine poroma.

Sexually-transmitted monkeypox: report of two cases.

Monkeypox is an emerging infection that has spread to all continents since May 2022. It is caused by the zoonotic monkeypox virus, consisting of double-stranded DNA, belonging to the Orthopoxvirus genus of the Poxviridae family, which has high transmissibility, especially by contact with the skin, favoring its sexual transmission. This case report describes a same-sex male couple, both aged 28 years old, without comorbidities. In the index case, perioral and penile lesions started ten days before the consultation, with rapid progression and a high fever that started eight days after the appearance of the lesions. In the second case, the perioral lesions started three days after the partner; however, he remained afebrile. Both were isolated, treated with symptomatic measures, and, after ulceration, the lesions completely regressed in 14 days. Dermatologists should be aware of manifestations of monkeypox, which may include vesiculopustular lesions in areas of sexual contact, as well as oligosymptomatic cases or cases with few skin lesions.

Pigmented eccrine poroma in an atypical location.

Eccrine poroma is the term that includes benign neoplasms of the terminal duct of the eccrine sweat glands, which may clinically and dermoscopically resemble other melanoma and non-melanoma skin tumors. They are often located on the extremities (especially palms and soles), presenting as normochromic or erythematous papules and nodules, measuring up to 2 cm. Pigmented variants are uncommon, accounting for less than 20% of cases. This report describes a 37-year-old man who developed a large pigmented eccrine poroma on his right shoulder, causing diagnostic difficulty. Histopathological examination revealed a nodular neoplasm consisting of small, monomorphic, cuboidal cells, with ample, eosinophilic cytoplasm and well-defined borders, in addition to conspicuous intercellular bridges, with melanin deposits diffusely distributed inside them. The absence of cytological atypia, cellular pleomorphism, increased mitotic activity, and necrosis foci corroborated the diagnostic exclusion of porocarcinoma, which can develop from eccrine poroma.

Treatment of Chronic Venous Ulcers With Heterologous Fibrin Sealant: A Phase I/II Clinical Trial.

Background: Heterologous fibrin sealant (HFS) consists of a fibrinogen-rich cryoprecipitate extracted from Bubalus bubalis buffalo blood and a thrombin-like enzyme purified from Crotalus durissus terrificus snake venom. This study evaluated the safety and immunogenicity of HFS, estimated the best dose, and assessed its preliminary efficacy in the treatment of chronic venous ulcers (CVU). Methods: A phase I/II non-randomized, single-arm clinical trial was performed on 31 participants, accounting for a total of 69 active CVUs. All ulcers were treated with HFS, essential fatty acid, and Unna boot for 12 weeks. The outcomes assessed were: (1) primary safety, immunogenicity analyses, and confirmation of the lowest safe dose; (2) secondary promising efficacy by analyzing the healing process. Immunogenicity was evaluated using the serum-neutralizing (IgM and IgG) and non-neutralizing (IgA and IgE) antibody techniques against the product. The immuno-detection of IgE class antibodies was assessed using dot-blot assay before and at the end of treatment. Positive samples on dot-blot assays were subsequently analyzed by western blotting to verify the results. Results: No severe systemic adverse events related to the use of HFS were observed. Local adverse events potentially related to treatment include ulcer pain (52%), peri-ulcer maceration (16%), peri-ulcer pruritus (12%), critical colonization (8%), peri-ulcer eczema (4%), the opening of new ulcers (4%), and increased ulcerated area 4%). Neutralizing and non-neutralizing antibodies did not show significant deviations at any of the evaluated time points. Blot assays showed that all patients presented negative immunological reactions, either before or after treatment, with the thrombin-like enzyme component. In addition, two participants showed a positive immunological reaction to the cryoprecipitate component, while another two were positive before and during treatment. Regarding the secondary outcomes of preliminary efficacy, a total healing and significant reduction of the area was observed in 47.5 and 22%, respectively. A qualitative improvement was observed in the wound beds of unhealed ulcers. Conclusions: The investigational HFS bioproduct proved to be safe and non-immunogenic with a good preliminary efficacy for the treatment of CVU, according to the protocol and doses proposed. A multicentric phase III clinical trial will be necessary to verify these findings.

Histiocitoma fibroso maligno no tornozelo: relato de caso / Malignant fibrous histiocytoma in ankle: case report

Histiocitoma fibroso maligno (MFH) ou sarcoma pleomórfico indiferenciado (UPS) é um sarcoma moderadamente agressivo, capaz de invadir estruturas adjacentes. Trata-se de neoplasia mesenquimal que predomina em homens entre a sexta e sétima décadas de vida. Localiza-se, principalmente, nos membros inferiores, podendo acometer cabeça e pescoço, tronco e retroperitônio, com tendência à recorrência e à metástase local. O presente relato tem como objetivo apresentar um caso de MFH no tornozelo de uma mulher de 49 anos, com invasão óssea adjacente, que evoluiu com amputação transtibial. São abordados aspectos clínicos, radiológicos, histopatológicos e terapêuticos, salientando-se a importância do diagnóstico precoce.

Malignant fibrous histiocytoma (MFH) or undifferentiated pleomorphic sarcoma (UPS) is a sarcoma capable of invading adjacent structures. It is a mesenchymal neoplasia that predominates in men between the sixth and seventh decades of life. It is located mainly in the lower limbs and may affect the head and neck, trunk, and retroperitoneum, presenting a tendency to recurrence and local metastasis. This report aims to present a case of MFH in the ankle of a 49-year-old woman with an adjacent bone invasion, which evolved with transtibial amputation. Clinical, radiological, histopathological, and therapeutic aspects were addressed, highlighting the importance of early diagnosis