Knee osteoarthritis (KOA) is a progressive and chronic musculoskeletal condition that continues to be the leading cause of disability worldwide. Conventional treatment approaches for the management of KOA largely focus on symptom alleviation rather than halting or reversing disease progression. However, recent advancements have highlighted the integrated interplay of mechanical stress, inflammation, cellular senescence, and chondrocyte dysfunction in the progression of KOA, in turn prompting new therapeutic strategies. Therefore, emerging interventions such as regenerative medicine, gene therapy, senolytic, platelet-rich plasma (PRP), disease-modifying osteoarthritis drugs (DMODs), and biologics have broadened the therapeutic options. Additionally, natural compounds demonstrated potential in KOA treatment with promising chondroprotective and anti-inflammatory effects.Moreover, digital technologies and clinical and molecular phenotyping enhanced early diagnosis, monitoring, and personalized management of the disease. Therefore, the current narrative review focuses on the molecular insights, clinical outcomes and prospects for the rapidly evolving landscape of current and emerging treatment approaches for the management of knee osteoarthritis (KOA).

Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, affecting millions annually and posing a significant global health concern. Traditional therapies for UTIs are becoming increasingly ineffective due to rising drug resistance and their tendency to disrupt the host's healthy microbiota, leading to further side effects. Consequently, there is an urgent need to develop alternative therapeutic agents that differ from conventional regimens and have fewer or no side effects. In this context, microbiome therapeutics offer a promising solution, given their demonstrated efficacy against various infectious diseases. Advances in scientific technology, particularly next-generation sequencing, have deepened our understanding of urinary microbiome dynamics, revealing a complex interplay within the urobiome that influences the onset and progression of UTIs. Uropathogenic bacteria do not solely cause UTIs; shifts in the composition of the urinary microbiome and interactions within the microbial community, known as host-microbiota interactions, also play a significant role. Although recent studies underscore the potential of targeting the urinary microbiome to manage UTIs and related complications, this field is still emerging and faces numerous regulatory and technical challenges. Further in-depth and comprehensive research is required to advance this pioneering concept into clinical practice.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, affecting millions annually and posing a significant global health concern. Traditional therapies for UTIs are becoming increasingly ineffective due to rising drug resistance and their tendency to disrupt the host's healthy microbiota, leading to further side effects. Consequently, there is an urgent need to develop alternative therapeutic agents that differ from conventional regimens and have fewer or no side effects. In this context, microbiome therapeutics offer a promising solution, given their demonstrated efficacy against various infectious diseases. Advances in scientific technology, particularly next-generation sequencing, have deepened our understanding of urinary microbiome dynamics, revealing a complex interplay within the urobiome that influences the onset and progression of UTIs. Uropathogenic bacteria do not solely cause UTIs; shifts in the composition of the urinary microbiome and interactions within the microbial community, known as host-microbiota interactions, also play a significant role. Although recent studies underscore the potential of targeting the urinary microbiome to manage UTIs and related complications, this field is still emerging and faces numerous regulatory and technical challenges. Further in-depth and comprehensive research is required to advance this pioneering concept into clinical practice.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, affecting millions annually and posing a significant global health concern. Traditional therapies for UTIs are becoming increasingly ineffective due to rising drug resistance and their tendency to disrupt the host's healthy microbiota, leading to further side effects. Consequently, there is an urgent need to develop alternative therapeutic agents that differ from conventional regimens and have fewer or no side effects. In this context, microbiome therapeutics offer a promising solution, given their demonstrated efficacy against various infectious diseases. Advances in scientific technology, particularly next-generation sequencing, have deepened our understanding of urinary microbiome dynamics, revealing a complex interplay within the urobiome that influences the onset and progression of UTIs. Uropathogenic bacteria do not solely cause UTIs; shifts in the composition of the urinary microbiome and interactions within the microbial community, known as host-microbiota interactions, also play a significant role. Although recent studies underscore the potential of targeting the urinary microbiome to manage UTIs and related complications, this field is still emerging and faces numerous regulatory and technical challenges. Further in-depth and comprehensive research is required to advance this pioneering concept into clinical practice.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, affecting millions annually and posing a significant global health concern. Traditional therapies for UTIs are becoming increasingly ineffective due to rising drug resistance and their tendency to disrupt the host's healthy microbiota, leading to further side effects. Consequently, there is an urgent need to develop alternative therapeutic agents that differ from conventional regimens and have fewer or no side effects. In this context, microbiome therapeutics offer a promising solution, given their demonstrated efficacy against various infectious diseases. Advances in scientific technology, particularly next-generation sequencing, have deepened our understanding of urinary microbiome dynamics, revealing a complex interplay within the urobiome that influences the onset and progression of UTIs. Uropathogenic bacteria do not solely cause UTIs; shifts in the composition of the urinary microbiome and interactions within the microbial community, known as host-microbiota interactions, also play a significant role. Although recent studies underscore the potential of targeting the urinary microbiome to manage UTIs and related complications, this field is still emerging and faces numerous regulatory and technical challenges. Further in-depth and comprehensive research is required to advance this pioneering concept into clinical practice.

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide, affecting millions annually and posing a significant global health concern. Traditional therapies for UTIs are becoming increasingly ineffective due to rising drug resistance and their tendency to disrupt the host's healthy microbiota, leading to further side effects. Consequently, there is an urgent need to develop alternative therapeutic agents that differ from conventional regimens and have fewer or no side effects. In this context, microbiome therapeutics offer a promising solution, given their demonstrated efficacy against various infectious diseases. Advances in scientific technology, particularly next-generation sequencing, have deepened our understanding of urinary microbiome dynamics, revealing a complex interplay within the urobiome that influences the onset and progression of UTIs. Uropathogenic bacteria do not solely cause UTIs; shifts in the composition of the urinary microbiome and interactions within the microbial community, known as host-microbiota interactions, also play a significant role. Although recent studies underscore the potential of targeting the urinary microbiome to manage UTIs and related complications, this field is still emerging and faces numerous regulatory and technical challenges. Further in-depth and comprehensive research is required to advance this pioneering concept into clinical practice.

This study aimed to evaluate the potential of hederacoside C, an active compound isolated from Hedera helix, which has been used for managing inflammatory respiratory diseases, in attenuating epidermal growth factor (EGF)-induced airway MUC5AC mucin gene expression. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with hederacoside C for 30 min and subsequently stimulated with EGF for 24 h. The study also examined the effect of hederacoside C on the EGF-induced mitogenactivated protein kinase (MAPK) signaling pathway. The results showed that hederacoside C inhibited MUC5AC mucin mRNA expression and the production of mucous glycoproteins by suppressing the phosphorylation of the EGF receptor (EGFR), as well as the phosphorylation of MAPK/extracellular signal-regulated kinase (ERK) 1/2 (MEK1/2), p38 MAPK, ERK 1/2 (p44/42), and the nuclear expression of specificity protein-1 (Sp1). These findings suggest that hederacoside C has the potential to reduce EGFinduced mucin gene expression by inhibiting the EGFR-MAPK-Sp1 signaling pathway in NCI-H292 cells.