Mangosteen (Garcinia mangostana L.), also known as the "queen of fruits", is a tropical fruit of the Clusiacea family. While native to Southeast Asian countries, such as Thailand, Indonesia, Malaysia, Myanmar, Sri Lanka, India, and the Philippines, the fruit has gained popularity in the United States due to its health-promoting attributes. In traditional medicine, mangosteen has been used to treat a variety of illnesses, ranging from dysentery to wound healing. Mangosteen has been shown to exhibit numerous biological and pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, antimalarial, antidiabetic, and anticancer properties. Disease-preventative and therapeutic properties of mangosteen have been ascribed to secondary metabolites called xanthones, present in several parts of the tree, including the pericarp, fruit rind, peel, stem bark, root bark, and leaf. Of the 68 mangosteen xanthones identified so far, the most widely-studied are α-mangostin and γ-mangostin. Emerging studies have found that mangosteen constituents and phytochemicals exert encouraging antineoplastic effects against a myriad of human malignancies. While there are a growing number of individual research papers on the anticancer properties of mangosteen, a complete and critical evaluation of published experimental findings has not been accomplished. Accordingly, the objective of this work is to present an in-depth analysis of the cancer preventive and anticancer potential of mangosteen constituents, with a special emphasis on the associated cellular and molecular mechanisms. Moreover, the bioavailability, pharmacokinetics, and safety of mangosteen-derived agents together with current challenges and future research avenues are also discussed.

Guava ( L.) tree (Myrtaceae family) bears fruit rich in vitamins, fiber, and other nutrients. While native to Latin America, guava is grown in many tropical and subtropical regions across the globe where it has long been used in traditional medicine to treat a myriad of ailments. Guava has been shown to exhibit a number of biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, and anticancer properties. Several parts of the plant, including the leaves, fruits, seeds, peels, pulp, bark, and oil, produce phytochemicals with medicinal properties. Emerging research has found that guava bioactive phytochemicals exert antitumorigenic effects against various human malignancies through multiple mechanisms. While there are numerous individual studies that document the anticancer effects of guava constituents, an up-to-date, comprehensive, and critical review of available research data has not been performed. Therefore, the purpose of this review is to present a complete analysis of the cancer preventive and anticancer therapeutic potential of guava-derived products and guava constituents, with a focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and toxicity of guava as well as limitations, challenges, and future directions of research have also been discussed.

Background:Despite recent advances in biologics, there is a lack of significant evidence regarding the comparative efficacy of biologics in treating more resistant features of psoriasis, namely nail psoriasis. A systematic review synthesizing data from multiple studies is efficacious in assessing the comparative efficacy among biologics for the treatment of nail psoriasis. Objective:To evaluate and compare the efficacy of biologics for the treatment of nail psoriasis. Methods:Utilizing PRISMA guidelines, a systematic literature review was conducted using the Pubmed database on November 16, 2022. Studies selected were phase 3 or 4 randomized clinical trials, clinical studies, or other randomized trials with data on the treatment with biologics for adults with nail psoriasis. Results:Sixteen studies meeting inclusion criteria were included for analysis. At 24 weeks, the highest mean NAPSI percent improvement achieved at week 24 was by brodalumab (76.9%) followed by etanercept (74%) and ixekizumab (70.5%) while the biologics achieving the greatest proportion of NAPSI 0 were adalimumab (44.6%) and ixekizumab (41%). Conclusions:This study helps elucidate the comparative efficacy of biologics for the treatment of nail psoriasis. This review suggests that brodalumab and etanercept are associated with the highest percent improvement in nail psoriasis while adalimumab and ixekizumab are associated with the greatest probability of complete nail resolution.

Erythema nodosum leprosum is an immunologic reaction that occurs in patients with lepromatous leprosy. We present the case of a 23-year-old female with a one-week history of fever and painful erythematous nodules along her upper and lower extremities. The patient had immigrated to the United States from Micronesia, where she was partially treated for leprosy two years prior. Histological examination from a punch biopsy demonstrated noncaseating granulomatous inflammation with numerous bacilli highlighted by the Fite stain. The acid-fast bacilli smear was positive. Given the patient's clinical, laboratory, and histological findings, a diagnosis of lepromatous leprosy with a type 2 erythema nodosum leprosum reaction was established. Multidrug antibiotic therapy with rifampin, dapsone, minocycline, and prednisone was initiated, following the addition of clofazimine. Early recognition and treatment of leprosy are crucial to preventing chronic and disabling complications, especially in instances of systemic inflammatory responses such as erythema nodosum leprosum.

BackgroundTumors often progress to a more aggressive phenotype to resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there is an emerging need to discover pivotal signaling pathways involved in the resistance to chemotherapeutic agents and cancer immunotherapy. Reports indicate the critical role of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like receptor pyrin domain-containing (NLRP) pathway in cancer initiation, progression, and development. Therefore, targeting TLR/NF-κB/NLRP signaling is a promising strategy to augment cancer chemotherapy and immunotherapy and to combat chemoresistance. Considering the potential of phytochemicals in the regulation of multiple dysregulated pathways during cancer initiation, promotion, and progression, such compounds could be suitable candidates against cancer chemoresistance.ObjectivesThis is the first comprehensive and systematic review regarding the role of phytochemicals in the mitigation of chemoresistance by regulating the TLR/NF-κB/NLRP signaling pathway in chemotherapy and immunotherapy.MethodsA comprehensive and systematic review was designed based on Web of Science, PubMed, Scopus, and Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to include papers on TLR/NF-κB/NLRP and chemotherapy/immunotherapy/chemoresistance by phytochemicals.ResultsPhytochemicals are promising multi-targeting candidates against the TLR/NF-κB/NLRP signaling pathway and interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, and sulfur compounds could be a promising strategy for managing cancer chemoresistance through the modulation of the TLR/NF-κB/NLRP signaling pathway. Novel delivery systems of phytochemicals in cancer chemotherapy/immunotherapy are also highlighted.ConclusionTargeting TLR/NF-κB/NLRP signaling with bioactive phytocompounds reverses chemoresistance and improves the outcome for chemotherapy and immunotherapy in both preclinical and clinical stages.

A 72-year-old female presented for evaluation of a lower eyelid lesion. She reported progressive enlargement of a skin colored papule over a year with rapid increase over the last several months. There was no reported inciting event, associated pain, bleeding, drainage, or visual changes. Her past medical history was notable for remote breast carcinoma with subsequent bilateral mastectomy. Physical examination revealed a firm 2.0 cm skin-colored nodule of the lower eyelid (Fig 1). An excisional biopsy was performed (Figs 2 and 3).Fig 2View Large Image Figure ViewerDownload Hi-res image Download (PPT)Fig 3View Large Image Figure ViewerDownload Hi-res image Download (PPT) Question 1: Based on the clinical presentation and histologic findings, what is the most likely diagnosis?A.Mucinous carcinomaB.Sebaceous carcinomaC.Basal cell carcinomaD.Endocrine mucin-producing sweat gland carcinomaE.Hidrocystoma Answers:A.Mucinous carcinoma – Correct. Primary cutaneous mucinous carcinoma is a rare adnexal tumor of the sweat gland that most commonly affects the eyelid. Histology shows a dermal tumor consisting of fibrous septae delineating pools of mucin with collections of basophilic epithelioid cells.1Tillit S.M. Iyer S.S.R. Grieser E.J. LiVecchi J.T. Treatment of recurrent primary cutaneous mucinous carcinoma of the eyelid with modified wide local excision.Case Rep Ophthalmol Med. 2020; 2020: 6668640https://doi.org/10.1155/2020/6668640Crossref PubMed Google ScholarB.Sebaceous carcinoma – Incorrect. While sebaceous carcinoma may clinically appear similar to mucinous carcinoma, the 2 can be differentiated histologically. In sebaceous carcinoma, histology reveals lobules of basaloid cells within the dermis with mitotic figures and necrosis.2Kyllo R.L. Brady K.L. Hurst E.A. Sebaceous carcinoma: review of the literature.Dermatol Surg. 2015; 41: 1-15https://doi.org/10.1097/DSS.0000000000000152Crossref PubMed Scopus (72) Google ScholarC.Basal cell carcinoma – Incorrect. Basal cell carcinoma is the most common cutaneous neoplasm and commonly occurs on the eyelid; however, nodes of uniform basaloid cells with stromal clefting arising from the epidermis would be present.D.Endocrine mucin-producing sweat gland carcinoma – Incorrect. Endocrine mucin-producing sweat gland carcinoma is a rare neuroendocrine derived tumor that most commonly presents on the periorbital skin. Histologically this is analogous to papillary breast carcinoma consistent with the similar embryologic origins of both sweat and mammary glands, and would display areas of solid and papillary growth.E.Hidrocystoma – Incorrect. Hidrocystomas are benign cystic proliferations of sweat glands that appear as blue to skin-colored dome-shaped papules or nodules. Characteristic histopathologic findings include a single or multiple cystic cavities within the dermis. Question 2: Additional workup or management should include which of the following?A.Immunohistochemical stainingB.ColonoscopyC.No further management is indicatedD.Warm compressE.Enucleation Answers:A.Immunohistochemical staining – Correct. When evaluating mucinous carcinoma, the major diagnostic concern is determining metastatic or primary cutaneous origin. Given this patient’s history of breast cancer, review of previous breast pathology and workup with immunohistochemical staining is warranted. Primary cutaneous mucinous carcinoma is positive for CK7 and negative for CK20, thyroid transcriotion factor-1, and D2-40,3Javaid H. Raza N. Ejaz U. Sarfraz T. Unusual skin mass (primary cutaneous mucinous carcinoma).BMJ Case Rep. 2018; 2018bcr2017222546PubMed Google Scholar which could help to exclude metastases from colon or other gastrointestinal sites and the lung. However, breast carcinoma displays a similar immunophenotype, and both primary cutaneous and metastatic breast mucinous carcinomas may also express estrogen receptor, progesterone receptor, GATA3, and p63, warranting the need for additional diagnostic imaging to exclude metastasis.B.Colonoscopy – Incorrect. Colonoscopy would be included in the diagnostic workup of sebaceous carcinoma when there is concern for associated Muir–Torre syndrome.C.No further management is indicated – Incorrect. This would not be an appropriate choice for mucinous carcinoma, as further workup and definitive management with surgical excision or radiation therapy is warranted.D.Warm compress – Incorrect. Warm compress is utilized for the conservative management of chalazion.E.Enucleation – Incorrect. Enucleation is used to treat uveal melanoma. Question 3: What histological findings would be seen in this patient?A.Collections of periodic acid–Schiff positive mucinB.Lobular dermal based sebaceous cellsC.Cystic space lined by a double layer of epithelial cellsD.Peripheral palisading with retraction from surrounding stromaE.Well demarcated papillated or cribriform nodules Answers:A.Collections of periodic acid–Schiff positive mucin – Correct. Mucinous carcinomas contain large collections of mucin that are periodic acid–Schiff positive and stains with colloidal iron, mucicarmine, and Alcian blue at a pH of 2.5. The mucin is classified as a sialomucin, a nonsulfated mucopolysaccharide that is resistant to hyaluronidase and diastase.4Chavez A. Linos K. Samie F.H. Primary cutaneous mucinous carcinoma of the eyelid treated with Mohs surgery.JAAD Case Rep. 2015; 1: 85-87https://doi.org/10.1016/j.jdcr.2015.02.002Abstract Full Text Full Text PDF PubMed Scopus (7) Google ScholarB.Lobular dermal based sebaceous cells – Incorrect. Lobular dermal based sebaceous cells with cytoplasmic lipid granules that stain positive with Oil-Red O and Sudan black are found in sebaceous carcinoma.C.Cystic space lined by a double layer of epithelial cells – Incorrect. Hidrocystomas appear histologically as unilocular or multilocular cystic spaces lined by a double layer of epithelial cells.D.Peripheral palisading with retraction from surrounding stroma – Incorrect. Peripheral palisading with retraction from surrounding stroma is a finding present in basal cell carcinomas.E.Well demarcated papillated or cribriform nodules – Incorrect. Cystic or solid well demarcated papillated or cribriform nodules are seen with Endocrine mucin-producing sweat gland carcinoma. Additionally, these tumors will most commonly stain positively for neuroendocrine markers including synaptophysin and chromogranin. Neuroendocrine immunohistochemistry helps to further differentiate from mucinous carcinoma.5Agni M. Raven M.L. Bowen R.C. et al.An update on endocrine mucin-producing sweat gland carcinoma: clinicopathologic study of 63 cases and comparative analysis.Am J Surg Pathol. 2020; 44: 1005-1016https://doi.org/10.1097/PAS.0000000000001462Crossref PubMed Scopus (21) Google Scholar None disclosed.

Immunoglobulin A (IgA) vasculitis is a small blood vessel vasculitis that is mediated by immune complex deposition. While it is the most common cause of childhood vasculitis, the disease is uncommon in adults with variable clinical manifestations. A 65-year-old female presented with a diffuse erythematous, pruritic, painful rash across her legs, back, and arms of 12 days' duration. Associated symptoms included fatigue, lower extremity swelling, and migratory arthralgias of the knees and ankles. Skin examination revealed edematous, blanchable, erythematous, annular papules and plaques on the legs, back, and arms with pitting edema of the lower legs. Laboratory testing revealed an elevated erythrocyte sedimentation rate, hypoalbuminemia, proteinuria, hematuria, and a positive antistreptolysin O titer, indicative of recent group A Streptococcus infection. Treatment with systemic corticosteroids led to a resolution of all her symptoms. Adult onset IgA vasculitis differs in clinical manifestation and treatment from that of the pediatric population. This case demonstrates the importance of considering IgA vasculitis as a differential diagnosis in adults presenting with small vessel vasculitis.

Pancreatic panniculitis is a rare cutaneous manifestation occurring in 0.3%-3% of patients with pancreatic diseases.1 The most common underlying etiology is pancreatitis, making up approximately 88% of cases, while pancreatic neoplasms account for the remaining 12%.2 Tender erythematous nodules localized to the lower extremities is the most common presentation. Extracutaneous findings include arthropathy, eosinophilia, osteolytic bone lesions, and serositis.3 When pancreatitis, panniculitis, and polyarthritis occur simultaneously (PPP), this triad is termed PPP syndrome.

Pyoderma gangrenosum (PG) is a rare, ulcerating, rapidly developing neutrophilic dermatosis that is often challenging to diagnose and treat. We present the case of a 47-year-old African American male who presented with a painful left anterior shin ulcer, fever, leukocytosis, and tachycardia. The patient had a similar lesion seven years prior that had since healed, with no other medical conditions. Sepsis secondary to a soft tissue infection was initially suspected; however, given the patient's history of pathergy, rapid progression of the lesion, skin examination, and sterile wound culture, PG was diagnosed. The patient improved in response to corticosteroid therapy. A brief overview of the disease presentation, diagnosis, and treatment is provided.

Hidradenocarcinomas are very uncommon malignant tumors of sweat gland origin that exhibit a high potential for local recurrence, metastasis, and poor outcome. These neoplasms typically resemble benign appearing dermal nodules that lack distinguishable features. We present the case of hidradenocarcinoma in a 39-year-old male with a 5-year history of a slow growing nodule along his right eyebrow. Excisional biopsy of the lesion was taken with pathology showing nuclear pleomorphism, increased mitoses, and foci of necrosis. Immunohistochemical analysis revealed reactivity for Ki-67/MIB1 and strong diffuse staining for p63, CK5/6, and CK7. Mohs micrographic surgery was performed and clear margins were obtained after one stage. Compared to traditional treatment with wide local excision, Mohs micrographic surgery is a potentially advantageous alternative therapy as there have been no reported cases of tumor recurrence or metastasis to date.

Despite the vast amounts of research and remarkable discoveries that have been made in recent decades, cancer remains a leading cause of death and a major public health concern worldwide. Gossypol, a natural polyphenolic compound derived from the seeds, roots, and stems of cotton (Gossypium hirsutum L.), was first used as a male contraceptive agent. Due to its diverse biological properties, including antifertility, antiviral, antioxidant, antibacterial, antimalarial, and most notably antitumor activities, gossypol has been the subject of numerous studies. Nevertheless, no systematic review has been performed that analyzes the antineoplastic potential of gossypol and related natural compounds in an organ-specific manner while delineating the molecular mechanisms of action. Hence, we have performed an extensive literature search for anticancer properties of gossypol and their natural derivatives against various types of cancer cells utilizing PubMed, ScienceDirect, Google Scholar, and Scopus. The sources, distribution, chemical structure, and toxicity of gossypol and its constituents are briefly reviewed. Based on emerging evidence, gossypol and related compounds exhibit significant antineoplastic effects against various cancer types through the modulation of different cancer hallmarks and signaling pathways. Additionally, the synergistic activity of gossypol and its derivatives with chemotherapeutic agents has been observed. Our evaluation of the current literature suggests the potential of gossypol and its derivatives as multitargeting drug candidates to combat multiple human malignancies.

Abstract Guava (Psidium guajava L.) tree (Myrtaceae family) bears fruit rich in vitamins, fiber, and other nutrients. While native to Latin America, guava is grown in many tropical and subtropical regions across the globe where it has long been used in traditional medicine to treat a myriad of ailments. Guava has been shown to exhibit a number of biological and pharmacological activities, such as antioxidant, anti-inflammatory, immunomodulatory, antimicrobial, antidiabetic, and anticancer properties. Several parts of the plant, including the leaves, fruits, seeds, peels, pulp, bark, and oil, produce phytochemicals with medicinal properties. Emerging research has found that guava bioactive phytochemicals exert antitumorigenic effects against various human malignancies through multiple mechanisms. While there are numerous individual studies that document the anticancer effects of guava constituents, an up-to-date, comprehensive, and critical review of available research data has not been performed. Therefore, the purpose of this review is to present a complete analysis of the cancer preventive and anticancer therapeutic potential of guava-derived products and guava constituents, with a focus on the cellular and molecular mechanisms of action. The bioavailability, pharmacokinetics, and toxicity of guava as well as limitations, challenges, and future directions of research have also been discussed.

Multiple dysregulated signaling pathways are implicated in the pathogenesis of cancer. The conventional therapies used in cancer prevention/treatment suffer from low efficacy, considerable toxicity, and high cost. Hence, the discovery and development of novel multi-targeted agents to attenuate the dysregulated signaling in cancer is of great importance. In recent decades, phytochemicals from dietary and medicinal plants have been successfully introduced as alternative anticancer agents due to their ability to modulate numerous oncogenic and oncosuppressive signaling pathways. Rutin (also known as rutoside, quercetin-3-O-rutinoside and sophorin) is an active plant-derived flavonoid that is widely distributed in various vegetables, fruits, and medicinal plants, including asparagus, buckwheat, apricots, apples, cherries, grapes, grapefruit, plums, oranges, and tea. Rutin has been shown to target various inflammatory, apoptotic, autophagic, and angiogenic signaling mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukins, light chain 3/Beclin, B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, caspases, and vascular endothelial growth factor. A comprehensive and critical analysis of the anticancer potential of rutin and associated molecular targets amongst various cancer types has not been performed previously. Accordingly, the purpose of this review is to present an up-to-date and critical evaluation of multiple cellular and molecular mechanisms through which the anticancer effects of rutin are known to be exerted. The current challenges and limitations as well as future directions of research are also discussed.

Abstract Hidradenocarcinomas are very uncommon malignant tumors of sweat gland origin that exhibit a high potential for local recurrence, metastasis, and poor outcome. These neoplasms typically resemble benign appearing dermal nodules that lack distinguishable features. We present the case of hidradenocarcinoma in a 39-year-old male with a 5-year history of a slow growing nodule along his right eyebrow. Excisional biopsy of the lesion was taken with pathology showing nuclear pleomorphism, increased mitoses, and foci of necrosis. Immunohistochemical analysis revealed reactivity for Ki-67/MIB1 and strong diffuse staining for p63, CK5/6, and CK7. Mohs micrographic surgery was performed and clear margins were obtained after one stage. Compared to traditional treatment with wide local excision, Mohs micrographic surgery is a potentially advantageous alternative therapy as there have been no reported cases of tumor recurrence or metastasis to date.