Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review.

Traditional medication and alternative therapies have long been used to treat breast cancer. One of the main problems with current treatments is that there is an increase in drug resistance in the cancer cells owing to genetic differences such as mutational changes, epigenetic changes and miRNA (microRNA) alterations such as miR-1246, miR-298, miR-27b and miR-33a, along with epigenetic modifications, such as Histone3 acetylation and CCCTC-Binding Factor (CTCF) hypermethylation for drug resistance in breast cancer cell lines. Certain forms of conventional drug resistance have been linked to genetic changes in genes such as ABCB1, AKT, S100A8/A9, TAGLN2 and NPM. This review aims to explore the current approaches to counter breast cancer, the action mechanism, along with novel therapeutic methods endowing potential drug resistance. The investigation of novel therapeutic approaches sheds light on the phenomenon of drug resistance including genetic variations that impact distinct forms of oestrogen receptor (ER) cancer, genetic changes, epigenetics-reported resistance and their identification in patients. Long-term effective therapy for breast cancer includes selective oestrogen receptor modulators, selective oestrogen receptor degraders and genetic variations, such as mutations in nuclear genes, epigenetic modifications and miRNA alterations in target proteins. Novel research addressing combinational therapies including maytansine, photodynamic therapy, guajadiol, talazoparib, COX2 inhibitors and miRNA 1246 inhibitors have been developed to improve patient survival rates.

Short-term, nonsurgical periodontal therapy boosts interleukin-12 levels and reduces oral cancer risk.

BACKGROUND: Cytokines, including interleukin-12 (IL-12), are proteins that regulate cell survival, proliferation, differentiation, and function. IL-12 is a heterodimeric proinflammatory cytokine. It possesses tumoricidal properties and promotes M1 macrophage polarization and IFN-γ production by T helper (Th1) cells, which in turn stimulates the antitumor cytotoxic cluster of eight positive (CD8+) and natural killer cells, therefore activating an effector immune response against tumor cells. MATERIALS AND METHODS: Herein, the IL-2 levels of 60 patients with generalized chronic periodontitis (GCP) were assessed. Plaque index, gingival index, pocket probing depth, bleeding on probing percentage (BOP %), and clinical attachment loss were the clinical indicators reported. RESULTS: Patients with GCP in the pretreatment group had substantially lower mean IL-12 levels than those in the post-treatment group. Short-term, nonsurgical treatment (NST) considerably improved periodontal indices and increased IL-12 levels, thereby reducing oral cancer risk. CONCLUSION: NST is a cost-effective and accessible cancer prevention procedure for general dentists.

Effect of PVP Molecular Weights on the Synthesis of Ultrasmall Cus Nanoflakes: Synthesis, Properties, and Potential Application for Phototheranostics.

Copper sulfide nanoparticles (CuS) hold tremendous potential for applications in photothermal therapy (PTT) and photoacoustic imaging (PAI). However, the conventional chemical coprecipitation method often leads to particle agglomeration issues. To overcome this challenge, we utilized polyvinylpyrrolidone (PVP) as a stabilizing agent, resulting in the synthesis of small PVP-CuS nanoparticles named PC10, PCK30, and PC40. Our study aimed to investigate how different molecular weights of PVP influence the nanoparticles' crystalline characteristics and essential properties, especially their photoacoustic and photothermal responses. While prior research on PVP-assisted CuS nanoparticles has been conducted, our study delves deeper into this area, providing insights into optical properties. Remarkably, all synthesized nanoparticles exhibited a crystalline structure, were smaller than 10 nm, and featured an absorbance peak at 1020 nm, indicating their robust photoacoustic and photothermal capabilities. Among these nanoparticles, PC10 emerged as the standout performer, displaying superior photoacoustic properties. Our photothermal experiments demonstrated significant temperature increases in all cases, with PC10 achieving an impressive efficiency of 51%. Moreover, cytotoxicity assays revealed the nanoparticles' compatibility with cells, coupled with an enhanced incidence of apoptosis compared to necrosis. These findings underscore the promising potential of PVP-stabilized CuS nanoparticles for advanced cancer theranostics.

Dermoscopy of hypopigmented macules unveiling genetic diagnosis of tuberous sclerosis complex type 2 in an infant presenting with sacral chordoma.

A 2-month-old male with surgically resected sacral chordoma presented with multiple hypopigmented macules showing characteristic patchy, sharply demarcated areas of pigment network on dermoscopy. These dermoscopic findings were suggestive of the ash-leaf macules of tuberous sclerosis over other common hypopigmented macules in neonates. Chordomas presenting in early childhood in the sacral location have been reported as a rare manifestation of tuberous sclerosis complex. The combination of these findings led to a diagnosis of tuberous sclerosis, confirmed with the finding of a heterozygous TSC2 gene deletion; treatment with sirolimus resulted in regression of cardiac rhabdomyomas and hypopigmented macules.

Utility of 18F-FDG PET/CT in Assessment of Disease Extent and Response to Treatment in Xanthoma Disseminatum.

The clinical utility of 18F-FDG PET/CT is being increasingly recognized in histiocytic disorders. We report the case of a 23-y-old woman who presented with slowly progressive, yellowish-brown papules, plaques, and nodules over her face and flexures. Besides the multiple cutaneous lesions, lesions of the brain, stomach, gallbladder, and marrow were additionally revealed by baseline 18F-FDG PET/CT. Skin biopsy and the overall clinical picture were consistent with xanthoma disseminatum. Subsequent PET/CT after cladribine therapy revealed a decrease in the extent and metabolic activity of most lesions, suggestive of a favorable response. This case report highlights the potential role of 18F-FDG PET/CT in the accurate assessment of disease extent and posttreatment response in rare histiocytic disorders.

The effect of non-surgical periodontal therapy on salivary IL-6 levels in patients with moderate to severe generalized chronic periodontitis.

BACKGROUND: Gene regulation of IL-6 is characterized by the presence of inflammatory cytokines, bacterial products, viral infection, and activation of the diacylglycerol-, cyclic AMP-, or Ca + + -activated signal transduction pathways. AIM: Scaling and root planning (SRP), a non-surgical periodontal therapy, was studied in connection to several clinical parameters for its effect on salivary IL-6 levels in patients with generalized chronic periodontitis. METHODS: For this study, a total of 60 GCP patients were included. Plaque index (PI), gingival index (GI), pocket probing depth (PPD), bleeding on probing percentage (BOP%), and clinical attachment loss were among the clinical indicators covered (CAL). RESULTS: Following SRP, mean IL-6 levels in patients with GCP were significantly higher in the pre-treatment group (2.93 5.17 pg/ml; p 0.05) than in the posttreatment group (5.78 8.26 pg/ml; baseline). Pre- and post-treatment IL-6 levels for PI (pre), BOP percent (pre/post), GI (post), and PPD were found to be positively correlated (post). In patients with GCP, the study showed a statistically significant correlation between periodontal metrics and salivary IL-6. CONCLUSIONS: Changes in periodontal indices and IL-6 levels that are statistically significant over time indicate that non-surgical treatment is effective, and IL-6 can be regarded as a potent disease activity marker.

Procedural dermatology and its unmet need.

Procedural dermatology includes invasive conventional dermatologic surgeries which involve significant use of knife and suture, minimally invasive procedures and device-based procedures. Device-based procedures are the easiest to learn and are less prone to human errors due to automation but can lead to monotony, while conventional surgeries require significant skill, craftsmanship and interest. There has been a recent shift in the approach to procedural dermatology as a therapeutic option with complementary and combination models replacing the conventional hierarchical model in which procedures were last in the step-ladder approach. The demand for both conventional dermatologic surgeries and minimally invasive cosmetic procedures is increasing. Unfortunately, this demand has not been met with adequate supply. Consequently, the number of trained professionals with expertise in these procedures is very limited; they are far outnumbered by unqualified practitioners. A limited number of dermatologic surgeons practicing conventional surgeries has resulted in huge waiting lists for vitiligo surgeries, inappropriate excisions for skin cancers and poor cosmetic outcomes of excisions without proper knowledge of flaps and grafts. Increasingly procedures are being performed by inadequately trained personnel, resulting in complications. There is also an absence of good quality research on the subject of procedural dermatology, which has resulted in a lack of standardisation of various procedures and knowledge about the efficacy of various drug-procedure and procedure-procedure combinations. An increasing variety of gimmicky but costly procedures are being offered to the public without much evidence of efficacy. Individual institutional and broad policy directives are needed to address these issues. Special emphasis is required on formal hands-on procedural dermatology training during residency and beyond it.

Current understanding of frictional dermatoses: A review.

Human skin is continually exposed to internal and external forces, dynamic as well as static. The skin is normally flexible and can resist mechanical trauma due to friction, pressure, vibration, suction and laceration to a considerable degree. However, an excess of these forces can abnormally affect the structure and function of the skin, setting the stage for the development of a skin disorder. Repetitive trauma can cause lichenification, hyperpigmentation, erythema, scaling, fissuring, blisters, ulceration and chronic alterations. Frictional dermatoses is an under-recognised entity with no clear-cut definition and encompasses a variety of terms such as frictional dermatitis, frictional melanosis, frictional pigmentary dermatoses and certain other named entities, many of which are confusing. The authors propose to define frictional dermatoses as 'a group of disorders caused by repetitive trauma to the skin as a result of friction of varied aetiology which can have a wide range of cutaneous manifestations depending on the type of insult.' The exact prevalence of frictional dermatoses as a separate entity is unknown. Authors who conducted this review include a group of dermatologists and post graduate students from various institutions. Literature was reviewed through PubMed, Medscape, Medline, ResearchGate and Google Scholar using the terms 'frictional dermatitis,' 'friction and skin,' 'dermatoses and culture,' 'clothing dermatitis,' 'friction melanosis,' 'PPE induced dermatoses in COVID-19 era,' etc. A total of 122 articles were reviewed and 100 articles among them were shortlisted and included in the study, after removing duplications. The review was followed up with further deliberation which resulted in the formulation of a new definition and classification of frictional dermatoses taking into account the morphology, histopathological characteristics, anatomical region affected and the major predisposing factors. The rising incidence of mechanical dermatoses in the COVID-19 era was also emphasised.

Role of Tunneling Nanotubes in Viral Infection, Neurodegenerative Disease, and Cancer.

The network of tunneling nanotubes (TNTs) represents the filamentous (F)-actin rich tubular structure which is connected to the cytoplasm of the adjacent and or distant cells to mediate efficient cell-to-cell communication. They are long cytoplasmic bridges with an extraordinary ability to perform diverse array of function ranging from maintaining cellular physiology and cell survival to promoting immune surveillance. Ironically, TNTs are now widely documented to promote the spread of various pathogens including viruses either during early or late phase of their lifecycle. In addition, TNTs have also been associated with multiple pathologies in a complex multicellular environment. While the recent work from multiple laboratories has elucidated the role of TNTs in cellular communication and maintenance of homeostasis, this review focuses on their exploitation by the diverse group of viruses such as retroviruses, herpesviruses, influenza A, human metapneumovirus and SARS CoV-2 to promote viral entry, virus trafficking and cell-to-cell spread. The later process may aggravate disease severity and the associated complications due to widespread dissemination of the viruses to multiple organ system as observed in current coronavirus disease 2019 (COVID-19) patients. In addition, the TNT-mediated intracellular spread can be protective to the viruses from the circulating immune surveillance and possible neutralization activity present in the extracellular matrix. This review further highlights the relevance of TNTs in ocular and cardiac tissues including neurodegenerative diseases, chemotherapeutic resistance, and cancer pathogenesis. Taken together, we suggest that effective therapies should consider precise targeting of TNTs in several diseases including virus infections.

Hypereosinophilic dermatitis: generalised lichenification and gyrate erythema as the sole manifestation of idiopathic hypereosinophilic syndrome.

A 22-year-old female presented with generalised lichenification and severe pruritus, along with multiple annular papules and concentric plaques over trunk and extremities for the last 3 years. Her haematological investigations revealed leucocytosis with peripheral blood eosinophilia and raised serum IgE levels. Skin biopsy showed perivascular and interstitial infiltrate of eosinophils and lymphocytes in the dermis. Bone marrow examination showed myeloid hypercellularity with increased number of eosinophils, but no atypical cells. Cytogenetic studies did not reveal any chromosomal alterations. No systemic involvement was found on imaging. A diagnosis of idiopathic skin-limited hypereosinophilic syndrome was made. She was treated with tapering doses of oral prednisolone and weekly methotrexate with significant improvement in skin lesions and pruritus in 2 months, which was maintained at 7-month follow-up.