Innovative Treatment Approaches Research Articles

Brief Report: Should a prior cancer history be reevaluated as an exclusion for clinical trial participation?

Clinical trials are designed to minimize factors capable of influencing patient outcomes beyond the specific diseases and treatments being studied; however, exclusion of prior cancer (PC) patients could potentially affect the generalizability of study results. We attempted to create a real-world proxy of recent immunotherapy trials in stage III and IV Non-Small Cell Lung Cancer (NSCLC) to understand the relevance of a PC history using the National Cancer Database. Patients diagnosed between 2017 and 2020 were stratified by the presence of a prior cancer history and propensity matched to compare receipt of immunotherapy with those who did not. We analyzed overall survival using Kaplan Meier analysis and Cox proportional hazards models. The addition of immunotherapy to a regimen of chemotherapy and radiation was associated with superior survival whether stage III NSCLC patients had a PC history (HR): 0.65 (95% CI 0.59, 0.71) or had no PC history (HR:0.69 95% CI: 0.66, 0.72). The addition of immunotherapy was also associated with superior survival for stage IV patients with a PC history (HR) 0.78 95% CI 0.72, 0.85) or without PC history (HR:0.75 95% CI: 0.73, 0.78). Examination of real-world outcomes of two practice-changing trial regimens found the innovative treatment approach to be superior, regardless of patient PC history. Risk for a second malignancy is a reality of improving cancer treatment, thus, to individualize treatment for patients based on their personal and tumor attributes, cancer survivors will need to be included in trials.

Treatment of recurrent tracheal adenoid cystic carcinoma with a covered airway stent loaded with Iodine-125 seeds: a 5-year follow-up case report

BackgroundThe treatment of recurrent tracheal adenoid cystic carcinoma (TACC), a rare pulmonary malignant tumor, typically involves bronchoscopic interventional therapy for patients ineligible for surgery or external radiotherapy. This report describes an innovative treatment approach for TACC, initially managed with interventional bronchoscopy and subsequently with a Y-shaped airway stent loaded with 125I seeds, following recurrence after 2 years.Case presentationA 50-year-old man presented with intermittent coughing for 2 months and was admitted to the hospital after the discovery of TACC a month earlier. Preoperative bronchial artery embolization was performed to reduce the risk of bleeding, followed by bronchoscopic tumor resection in January 2017 using an electric loop at the base, complemented by argon plasma coagulation (APC) and cryotherapy. Although short-term outcomes were favorable, the long-term prognosis remained suboptimal. Due to tumor recurrence, airway tumor resection and implantation of the 125I seed stent were performed under bronchoscope guidance in early 2019. The stent was removed 5 months later. The patient tolerated the procedure well and exhibited no signs of relapse or progression during the 5-year postoperative follow-up period. This case illustrates the successful application of a stent loaded with 125I seeds for treating unresectable TACC.ConclusionsTreatment of TACC with a covered airway stent loaded with 125I seeds may be a safe, effective, and scalable method.

Comparison of a fixed-dose combination of Celecoxib/PG201 [Layla®] versus co-administration of individual formulations in healthy participants: A randomized trial.

Osteoarthritis (OA) is a prevalent joint disease affecting the spine, hands, hips, knees, and feet. However, definitive drugs for OA are lacking, and current treatments are limited owing to inconvenient administration, inadequate functional improvement, and long-term side effects including gastrointestinal and cardiovascular adverse events. Therefore, in this study, we aimed to assess the pharmacokinetics and safety profiles of PK101, a fixed-dose combination (FDC) comprising PG201, a 12-herb extract used in OA treatment in traditional East Asian medicine, and celecoxib, a selective cyclooxygenase-2 inhibitor, by comparing its administration as an FDC and the corresponding individual formulations in healthy subjects. A randomized, open-label, single-dose, 2 × 2 crossover design with a cohort of healthy participants. All subjects received a single FDC tablet (405.4 mg PG201 and 100 mg celecoxib) or the individual formulations, with 7-day washout period between administrations. The estimation of maximum plasma concentration and area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration of celecoxib involved determining the geometric mean ratios and 90% confidence intervals of the FDC compared to its individual formulations. Forty-six participants were enrolled; however, only 44 completed the study. The geometric mean ratios (90% confidence intervals) for the area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration and maximum plasma concentration of celecoxib were 1.1124 (1.0601-1.1672) and 1.2788 (1.1708-1.3969), respectively. The time of maximum plasma concentration range was 1.0 to 4.0 hours and 1.0 to 6.0 hours (minimum-maximum) for the FDC and individual formulations, respectively. Seven adverse events occurred in 6 subjects. The systemic exposure and safety profiles of the individual and FDC formulations were similar, supporting their potential as an innovative and effective therapeutic approach for OA treatment. All relevant data are within the paper and its Supporting Information files.

The utilization of CRISPR-Cas9 with human pluripotent stem cell for Parkinson's disease modeling

Abstract. Parkinson's disease (PD), also often referred to as "parkinsonism," is a neurodegenerative disorder. Those afflicted with this condition are frequently elderly, which results in a considerable decline in their quality of life and overall well-being. Although there are major breakthroughs in PD research, there remains an incomplete grasp of the disease's pathogenesis and the formulation of innovative treatment approaches. This has led to an urgent need for a technology that can recapitulate all the features of human PD. The emergence of induced pluripotent stem cells (iPSC) coupled with the rising appeal of Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9 (CRISPR-Cas9) technology, the construction of PD models through the combination of iPSC and CRISPR-Cas9 has emerged as a crucial area of research in the field of PD. Employing patients' somatic cells, transformed into iPSC and integrated with CRISPR-Cas9 for genetic modification, has facilitated the duplication of the genetic makeup of neural cells associated with PD, thereby facilitating the investigation of the influence of diverse genotypes on disease progression and treatment response. This review outlines the application and future development of iPSC and CRISPR-Cas9 technologies for the study of Parkinson's disease pathogenesis. The technology enables scientists to gain a deeper understanding of PD and paves the way for the development of novel therapeutic approaches in the future.

The Use of Slack Variables in the Adjoint Method Handling Inequality Constraints in Optimal Control and the Application to Tumor Drug Dosage

Abstract In this article a modified gradient approach, based on the adjoint method, is introduced, to deal with optimal control problems involving inequality constraints. So far, the only way to incorporate inequality constraints in the adjoint approach, is to introduce additional penalty terms in the cost functional. However, this may distort the optimal control due to weighting factors required for these terms and raise serious concerns about the magnitude of the weighting factors. The method in this article avoids penalty functions and can be used for the iterative computation of optimal controls. In order to demonstrate the key idea, first, a static optimization problem in the Euclidean space is considered. Second, the presented approach is applied to the tumor anti-angiogenesis optimal control problem in medicine, which addresses an innovative cancer treatment approach that aims to inhibit the formation of the tumor blood supply. The tumor anti-angiogenesis optimal control problem with free final time involves inequality and final constraints for control and state variables and is solved by a modified adjoint gradient method introducing slack variables. It has to be emphasized that the novel formulation and the special use of slack variables in this article delivers high accurate solutions without distorting the optimal control.

Type I Interferon Drives a Cellular State Inert to TCR-Stimulation and Could Impede Effective T-Cell Differentiation in Cancer.

Head and neck squamous cell carcinoma (HNSCC) is linked to human papillomavirus (HPV) infection. HPV-positive and HPV-negative HNSCC exhibit distinct molecular and clinical characteristics. Although checkpoint inhibitors have shown efficiency in recurrent/metastatic HNSCC, response variability persists regardless of HPV status. This study aimed to explore the CD8+ T-cell landscape in HPV-negative HNSCC. We performed simultaneous single-cell RNA and TCR sequencing of CD8+ tumor-infiltrating lymphocytes (TILs) from treatment-naïve HPV-negative HNSCC patients. Additionally, cells were stimulated ex vivo, which allowed for the tracking of clonal transcriptomic responses. Our analysis identified a subset of CD8+ TILs highly enriched for interferon-stimulated genes (ISG). TCR analysis revealed ISG cells are clonally related to a population of granzyme K (GZMK)-expressing cells. However, unlike GZMK cells, which exhibited rapid effector-like phenotypes following stimulation, ISG cells were transcriptionally inert. Additionally, ISG cells showed specific enrichment within tumor and were found across multiple tumor entities. ISG-enriched CD8+ TILs are a consistent feature of various tumor entities. These cells are poorly understood but possess characteristics that may impact antitumor immunity. Understanding the unique properties and functionality of ISG cells could offer innovative treatment approaches to improve patient outcomes in HPV-negative HNSCC and other cancer types.

Exploring non-canonical targets in Alzheimer’s disease: a departure from the norm

AbstractAlzheimer’s disease (AD), a progressive neurodegenerative disorder, is characterized by neurological impairments such as visual and sensory difficulties, motor dysfunction, sphincter issues, incoordination, gait abnormalities, and cognitive decline. Despite advances in understanding AD pathophysiology and the expansion of therapeutic options over the past three decades, the disease remains incurable. Current therapies, even those specifically targeting AD, often fail to significantly alter its progression, underscoring the need for innovative treatment approaches beyond symptomatic relief. This calls for a re-examination of AD pathology to identify potential therapeutic targets that go beyond conventional strategies. This review highlights four of the most promising non-canonical therapeutic targets: oligodendrocytes, the blood–brain barrier (BBB), neuroimmunometabolism, and the coagulation system. These components are crucial for maintaining the integrity and proper function of neurons and the brain, playing key roles in the progression of AD. Oligodendrocytes, for example, are essential for myelination and neuronal support, while BBB dysfunction can lead to impaired clearance of toxic proteins. Neuroimmunometabolism offers insights into how metabolic processes influence immune responses in the brain and dysregulation of the coagulation system has been linked to increased neuroinflammation and vascular abnormalities in AD. Recent discoveries in these fields provide new avenues for understanding the disease and identifying potential therapeutic targets. By exploring these non-canonical pathways, future research may offer breakthroughs in treating AD, moving beyond symptomatic management towards disease-modifying strategies.

A pan-cancer study of ADAM9’s immunological function and prognostic value particularly in liver cancer

A pan-cancer analysis summarizing the overall changes in mRNA and protein stability of ADM9, as well as its oncogenic function on immune cell line modulation and checkpoints within the tumor microenvironment (TME), is lacking, despite the fact that ADM9 up-regulation is correlated with the progression of many cancers. Therefore, in this study, we comprehensively analyzed the role of ADAM9 expression and its prognostic value in different cancers to fill this gap. Multiple bioinformatics databases such as Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to evaluate the ADAM9 genetic alternation, phosphorylation, and methylation, and indicated highly positive correlated genes that might play a critical interaction with ADAM9 and their molecular function with GO analysis. We also evaluate the effect of higher ADAM9 with prominent immune modulatory genes and immune infiltration especially in liver cancer pathogenesis stimulates lower NK cell effector functions based on its role in MICA shedding and increasing the Tregs infiltration. Immunohistochemistry (IHC) staining from 90 pathologically verified samples proved the positive correlation between ADAM9 and tumor stages and proved the higher expression of ADAM9 correlated genes (SNX9, APP, TNF, CDH1, ITGAV, MAD2L2) in HCC pathogenesis. In conclusion, this pan-cancer study provides a comprehensive understanding of the prognostic value of ADAM9 in various tumors emphasizing its importance to be considered as an innovative treatment approach, especially in tumor immunity shortly.

Advanced Nanomaterials for Cancer Therapy: Gold, Silver, and Iron Oxide Nanoparticles in Oncological Applications.

Cancer remains one of the most challenging health issues globally, demanding innovative therapeutic approaches for effective treatment. Nanoparticles, particularly those composed of gold, silver, and iron oxide, have emerged as promising candidates for changing cancer therapy. This comprehensive review demonstrates the landscape of nanoparticle-based oncological interventions, focusing on the remarkable advancements and therapeutic potentials of gold, silver, and iron oxide nanoparticles. Gold nanoparticles have garnered significant attention for their exceptional biocompatibility, tunable surface chemistry, and distinctive optical properties, rendering them ideal candidates for various cancer diagnostic and therapeutic strategies. Silver nanoparticles, renowned for their antimicrobial properties, exhibit remarkable potential in cancer therapy through multiple mechanisms, including apoptosis induction, angiogenesis inhibition, and drug delivery enhancement. With their magnetic properties and biocompatibility, iron oxide nanoparticles offer unique cancer diagnosis and targeted therapy opportunities. This review critically examines the recent advancements in the synthesis, functionalization, and biomedical applications of these nanoparticles in cancer therapy. Moreover, the challenges are discussed, including toxicity concerns, immunogenicity, and translational barriers, and ongoing efforts to overcome these hurdles are highlighted. Finally, insights into the future directions of nanoparticle-based cancer therapy and regulatory considerations, are provided aiming to accelerate the translation of these promising technologies from bench to bedside.

Prof. G Srinivasa Acharya: A guiding light and a skilled practitioner

Abstract This article aims to shed light on the substantial contributions made by renowned visionary Dr. G. Srinivas Acharya in the field of Ayurveda. Dr. Acharya’s journey has been characterized by dedication, hard work, and a relentless pursuit of knowledge. With a strong grounding in Ayurvedic principles, he has been instrumental in bridging the gap between ancient wisdom and modern science. Dr. Acharya’s expertise in treating a wide range of diseases is truly remarkable. From autoimmune disorders to cancer, diabetes, hypertension, arthritis, skin conditions, neurological disorders, stress management, rejuvenation therapies, and more, he has made a lasting impact on the lives of countless patients. His expertise in employing Rasayana Chikitsa for the treatment of challenging cases has been particularly noteworthy. Beyond his clinical practice, his tireless efforts in promoting Ayurveda at international forums and establishing collaborations with leading universities and institutions have played a significant role in raising awareness about this ancient medical system. By sharing his knowledge and inspiring others, he has contributed to the growth and recognition of Ayurveda on a global scale. His dedication to the field of Ayurveda, coupled with his innovative approach and expertise in treatment, has earned him a place of prominence among the visionaries who have dedicated themselves to this ancient science.

Edge advances in nanodrug therapies for osteoarthritis treatment.

As global population and lifestyles change, osteoarthritis (OA) is becoming a major healthcare challenge world. OA, a chronic condition characterized by inflammatory and degeneration, often present with joint pain and can lead to irreversible disability. While there is currently no cure for OA, it is commonly managed using nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and glucosamine. Although these treatments can alleviate symptoms, it is difficult to effectively deliver and sustain therapeutic agents within joints. The emergence of nanotechnology, particularly in form of smart nanomedicine, has introduced innovative therapeutic approaches for OA treatment. Nanotherapeutic strategies offer promising advantages, including more precise targeting of affected areas, prolonged therapeutic effects, enhanced bioavailability, and reduced systemic toxicity compared to traditional treatments. While nanoparticles show potential as a viable delivery system for OA therapies based on encouraging lab-based and clinical trials results, there remails a considerable gap between current research and clinical application. This review highlights recent advances in nanotherapy for OA and explore future pathways to refine and optimize OA treatments strategies.

Study on an Integrated Water Treatment System by Simultaneously Coupling Granular Activated Carbon (GAC) and Powdered Carbon with Ultrafiltration

The process of using powdered activated carbon (PAC) in conjunction with ultrafiltration (UF) has been widely adopted for the treatment of various types of water and wastewater. However, during the application of this integrated PAC-UF process, PAC tends to adhere significantly to the surface of the UF membrane, which exacerbates membrane fouling. To tackle this issue, this study proposed an innovative water treatment approach that simultaneously integrated granular activated carbon (GAC) and PAC/biochar with UF. In this setup, PAC/biochar was intended to enhance water quality, while the fluidized GAC particles were aimed at reducing membrane fouling and the deposition of PAC/biochar on the membrane surface. We systematically analyzed the operational performance of the integrated systems concerning fouling formation, PAC/biochar attachment, effluent quality, and foulant components. The results indicate that both PAC and biochar effectively improved effluent quality in terms of chemical oxygen demand (COD) and hardness, although they significantly deposited on the membrane surface during operation. Notably, PAC was more prone to attach to the membrane than biochar, and the fouling in biochar-UF systems was primarily attributed to the attachment of organic foulants rather than biochar itself. By combining with GAC, up to 46.01% of membrane fouling and 96.11% of PAC/biochar attachment were mitigated due to the strong mechanical action of the fluidized GAC particles. Importantly, the inclusion of fluidized GAC did not significantly affect effluent quality. Consequently, the GAC-PAC/biochar systems proposed in this study demonstrated dual benefits of improving effluent quality and ensuring stable operation, thereby providing a viable solution for efficient and sustainable water treatment.

Targeting PGK1: A New Frontier in Breast Cancer Therapy Under Hypoxic Conditions

Breast cancer represents one of the most prevalent malignant neoplasms affecting women, and its pathogenesis has garnered significant scholarly interest. Research indicates that the progression of breast cancer is intricately regulated by glucose metabolism. Under hypoxic conditions within the tumor microenvironment, breast cancer cells generate ATP and essential biosynthetic precursors for growth via the glycolytic pathway. Notably, phosphoglycerate kinase 1 (PGK1) is intimately associated with the regulation of hypoxia-inducible factors in breast cancer and plays a crucial role in modulating glycolytic processes. Further investigation into the role of PGK1 in breast cancer pathogenesis is anticipated to identify novel therapeutic targets and strategies. This review consolidates current research on the regulation of glucose metabolism and the function of PGK1 in breast cancer within hypoxic conditions. It aims to offer a significant theoretical foundation for elucidating the mechanisms underlying breast cancer progression and metastasis, thereby facilitating the development of innovative treatment approaches.

Targeting an altered sphingolipid profile with consecutive lipotoxicity as therapeutic approach to calcific aortic valve disease

Abstract Background Aortic stenosis due to calcific aortic valve disease (CAVD) is the most common valvular heart disease. In symptomatic patients, without repair the prognosis is poor. Treatment to date is based on surgery or catheter-based interventions. Pharmacological therapy options to prevent the progression of valve calcification are not available. In vascular smooth muscle cells, cellular accumulation of sphingolipids is associated with a proinflammatory response in the sense of lipotoxicity. Chronic inflammatory processes are indeed also essential for aortic valve calcification. Purpose With the subsequent goal of developing innovative treatment approaches for CAVD, we therefore aim to elucidate the unclear role of sphingolipids in the development of CAVD. Methods Human aortic valve and plasma samples of CAVD patients and controls (n=26) were analysed by liquid chromatography–mass spectrometry for lipidomics and proteomics. Human aortic valve interstitial cells (hVICs) were stimulated with ceramides. Calcification was detected by alizarin red staining. mRNA expression of bone-related proteins was determined by qPCR. NF-kB pathway was assessed by proteome profiler. Myriocin and GW4869 were applied to inhibit ceramide biosynthesis. PDTC and MCC950 were used to inhibit NF-kB Pathway and NLRP3 activation. ApoE-/- mice received a gain-of-function PCSK9 adeno-associated virus vector and fed high cholesterol diet for 14 weeks. Myriocin was applied orally over the treatment period to inhibit ceramide de novo synthesis in vivo. Murine echocardiography was used to measure transvalvular velocity and left ventricular function. Calcification degree of murine aortic valve was determined by histological staining. Results A significantly altered sphingolipid profile was observed in aortic valve tissue of CAVD patients (Fig. 1). Ceramide species e.g. Cer (17:1;2O/16:0) were increased. Verifying the biological relevance of these findings in vitro, C2-Cer (d18:1/2:0) enhanced hVIC calcification (Fig. 2). Accordingly, ALP activity and mRNA expression of osteogenic genes RUNX2, ALPL and MSX2 were increased. Furthermore, C2-Cer (d18:1/2:0) enhanced NF-kB p65 phosphorylation and NLRP3 activation, while treatment with both PDTC and MCC950 protected against C2-Cer (d18:1/2:0) induced calcification. Supporting the role of sphingolipid biosynthesis in hVIC calcification, Myriocin and GW4869 both reduced ox-LDL-induced VIC calcification which was reversed by C2-Cer(d18:1/2:0). Finally, Myriocin reduced the degree of calcification and transvalvular jet velocity of aortic valve in the PCSK9-AAV ApoE-/- mice model. Conclusion CAVD is accompanied by an accumulation of ceramides causing lipotoxicity in human aortic valve tissue. Pharmacological modulation of sphingolipid metabolism is an effective approach to prevent the development and progression of aortic valve calcification in vivo and should be considered as a future therapeutic strategy in CAVD patients.Volcano Plot of CAVD tissue lipidomicsC2 Ceramide enhances hVIC calcification

Phytochemical Compounds as Promising Therapeutics for Intestinal Fibrosis in Inflammatory Bowel Disease: A Critical Review.

Intestinal fibrosis, a prominent consequence of inflammatory bowel disease (IBD), presents considerable difficulty owing to the absence of licensed antifibrotic therapies. This review assesses the therapeutic potential of phytochemicals as alternate methods for controlling intestinal fibrosis. Phytochemicals, bioactive molecules originating from plants, exhibit potential antifibrotic, anti-inflammatory, and antioxidant activities, targeting pathways associated with inflammation and fibrosis. Compounds such as Asperuloside, Berberine, and olive phenols have demonstrated potential in preclinical models by regulating critical signaling pathways, including TGF-β/Smad and NFκB, which are integral to advancing fibrosis. The main findings suggest that these phytochemicals significantly reduce fibrotic markers, collagen deposition, and inflammation in various experimental models of IBD. These phytochemicals may function as supplementary medicines to standard treatments, perhaps enhancing patient outcomes while mitigating the adverse effects of prolonged immunosuppressive usage. Nonetheless, additional clinical trials are necessary to validate their safety, effectiveness, and bioavailability in human subjects. Therefore, investigating phytochemicals may lead to crucial advances in the formulation of innovative treatment approaches for fibrosis associated with IBD, offering a promising avenue for future therapeutic development.

TFEB signaling promotes autophagic degradation of NLRP3 to attenuate neuroinflammation in diabetic encephalopathy.

Diabetic encephalopathy (DE), a neurological complication of diabetes mellitus, has an unclear etiology. Shreds of evidence show that the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome-induced neuroinflammation and transcription factor EB (TFEB)-mediated autophagy impairment may take part in DE development. The crosstalk between these two pathways and their contribution to DE remains to be explored. A mouse model of type 2 diabetes mellitus (T2DM) exhibiting cognitive dysfunction was created, along with high glucose (HG) cultured BV2 cells. Following, 3-methyladenine (3-MA) and rapamycin were utilized to modulate autophagy. To evaluate the potential therapeutic benefits of TFEB in DE, we overexpressed and knocked down TFEB in both mice and cells. Autophagy impairment and NLRP3 inflammasome activation were noticed in T2DM mice and HG-cultured BV2 cells. The inflammatory response caused by NLRP3 inflammasome activation was decreased by rapamycin-induced autophagy enhancement, while 3-MA treatment further deteriorated it. Nuclear translocation and expression of TFEB were hampered in HG-cultured BV2 cells and T2DM mice. Exogenous TFEB overexpression boosted NLRP3 degradation via autophagy, which in turn alleviated microglial activation as well as ameliorated cognitive deficits and neuronal damage. Additionally, TFEB knockdown exacerbated neuroinflammation by decreasing autophagy-mediated NLRP3 degradation. Our findings have unraveled the pathogenesis of a previously underappreciated disease, implying that the activation of NLRP3 inflammasome and impairment of autophagy in microglia are significant etiological factors in the DE. The TFEB-mediated autophagy pathway can reduce neuroinflammation by enhancing NLRP3 degradation. This could potentially serve as a viable and innovative treatment approach for DE.

Astragalus membranaceus: A Traditional Chinese Medicine with Multifaceted Impacts on Breast Cancer Treatment

Breast cancer, the most prevalent malignant tumor among women globally, remains a critical area of focus for researchers striving to refine therapeutic approaches. As an important component of traditional Chinese medicine, Astragalus membranaceus (AM) has demonstrated potential for multifaceted impacts on breast cancer treatment through various mechanisms. To guide clinical practice and further explore the under-researched field of AM in breast cancer treatment, this paper mainly reviews the regulatory roles of AM-derived compounds and extracts on breast cancer cell proliferation, migration, invasion, and chemoresistance. Furthermore, this study delves into the synergistic effects observed when AM is co-administered with chemotherapeutic agents, including the enhancement of chemosensitivity, mitigation of toxic side effects, and reversal of drug resistance. This review indicates that AM holds promise not only as a therapy in breast cancer treatment but also paves the way for innovative integrated treatment approaches that combine the benefits of traditional medicine with modern pharmaceuticals. Nevertheless, future research endeavors are also urged to elucidate the in vivo pharmacological effects and underlying mechanisms of AM to inform more effective clinical treatment strategies.

Sinonasal Squamous Cell Carcinoma in the Netherlands: APopulation-Based Study of 568 Cases Diagnosed in 2008-2021.

Sinonasal squamous cell carcinoma is known for its rarity and poor prognosis. This study aims to investigate the trends in the incidence of sinonasal squamous cell carcinoma in the Netherlands and to analyze patient characteristics and treatment practices in order to assess their relation with patient outcomes. In this prospectively designed population-based cohort study, all patients diagnosed with sinonasal squamous cell carcinoma between 2008 and 2021 in the Netherlands were included. Patients with a squamous cell carcinoma of the nasal vestibule were excluded, leading to a definitive study population of 568 cases. The annual incidence rate for the overall population displayed a slight upward trend over the inclusion period with an annual percentage change of 1.6%. The 5-year overall, disease-free, and relative survival were 43.0%, 52.0%, and 47.2%, respectively. Relative survival decreased marginally over the course of the inclusion period. Sinonasal squamous cell carcinoma is rare with approximately stable incidence rates. There is a limited, non-statistically significant, decrease in survival between 2008 and 2021. Therefore, there is a clear need for innovative treatment approaches to improve outcomes for patients with sinonasal squamous cell carcinoma.

Cannabis use disorder: from neurobiology to treatment.

Cannabis has been legalized for medical and recreational purposes in multiple countries. A large number of people are using cannabis and some will develop cannabis use disorder (CUD). There is a growing recognition that CUD requires specific interventions. This Review will cover this topic from a variety of perspectives, with a particular emphasis on neurobiological findings and innovative treatment approaches that are being pursued. We will first describe the epidemiology and burden of disease of CUD, including risk factors associated with CUD (both in terms of general risk and genetic risk variants). Neurobiological alterations identified in brain imaging studies will be presented. Several psychosocial interventions that are useful for the management of CUD, including motivational enhancement therapy, behavioral and cognitive therapy, and contingency management, will be covered. Although no pharmacological interventions are yet approved for CUD, we present the most promising pharmacological interventions being tested.

Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.

Neuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.