Osteoporosis (OP) is a systemic skeletal disorder characterized by decreased bone mineral density (BMD), impaired bone microarchitecture, and an elevated risk of fragility fractures. Although conventional pharmacological agents—such as bisphosphonates, selective estrogen receptor modulators, and monoclonal antibodies—can attenuate disease progression, their long-term application is limited by adverse effects and suboptimal patient adherence. Consequently, there is growing interest in the development of safer, multi-targeted therapeutic strategies. Plant-derived bioactive products have garnered increasing attention due to their broad pharmacological profiles, including the promotion of osteoblastogenesis, suppression of osteoclastogenesis, regulation of bone–vascular coupling, and modulation of immune and oxidative stress pathways. Recent advances in biomaterial-assisted delivery systems have further improved the physicochemical stability, bioavailability, and tissue-specific delivery of these phytochemicals, thereby enhancing their therapeutic efficacy in bone regeneration. Although accumulated in vitro and in vivo studies suggest the bone-protective potential of these natural agents, clinical translation remains limited. Further mechanistic investigations and rigorously designed clinical trials are warranted to substantiate their efficacy and safety in human populations. This review summarizes recent progress in the mechanistic understanding of natural products involved in bone metabolism, with a particular focus on representative classes such as flavonoids, polyphenols, polysaccharides, glycosides, and terpenoids. In addition, we discuss the translational potential of integrating these agents with advanced drug delivery platforms, aiming to provide a theoretical framework and future research directions for the treatment of OP and related bone disorders.

Osteoporosis is a systemic skeletal disorder characterized by progressive loss of bone mass and deterioration of microarchitectural integrity. Traditionally, its pathogenesis has been attributed primarily to an imbalance in the number and activity of osteoblasts and osteoclasts. However, emerging evidence has uncovered a critical bidirectional interdependence between the integrity of the extracellular matrix (ECM) and the functional homeostasis of the intracellular lysosomal system—an axis increasingly recognized as the “bone matrix–lysosome crosstalk.” Despite its apparent importance, the central role of this regulatory circuitry in bone homeostasis and the mechanisms through which it becomes disrupted under pathological conditions remain insufficiently defined.This review synthesizes current advances regarding the cell type–specific functions of lysosomes across distinct bone cell populations and further examines how the ECM, as a dynamic microenvironment, exerts reciprocal control over lysosomal biogenesis and activity. We highlight how the biochemical composition and biophysical properties of the ECM govern lysosomal acidification, metabolic coupling, and degradative capacity with remarkable precision. During the progression of osteoporosis, structural compromise of the ECM and lysosomal dysfunction reinforce one another, establishing a self-amplifying pathological loop that accelerates the collapse of the bone microenvironment. Recognizing this reciprocal deterioration, we propose that restoring the dynamic equilibrium of the “ECM–lysosome axis” may represent a mechanistic pivot for reversing osteoporotic degeneration. Interventions targeting lysosomal function, reconstructing the bone ECM, and employing nanomedicine-enabled organelle-specific delivery hold particular promise for advancing precision therapeutics in osteoporosis.

Osteoporosis is a metabolic bone disease characterized by the loss and destruction of bone microstructure. Its incidence rate increases with age and is an important public health problem. Recently, the relationship between lipid metabolism and osteoporosis has received widespread attention. Lipid metabolites, such as fatty acids, cholesterol, and adipose tissue-derived hormones, participate in maintaining bone metabolism homeostasis through key molecular networks that regulate bone cell function. In addition, the interaction between lipid metabolism and bone tissue involves cross-organ regulatory mechanisms, including the bone-adipose, bone-pancreas, and bone-gut axes. This study considers the types of lipid metabolites and their effects on bone cell function as a starting point for exploring the interaction between lipid metabolism and bone tissue. Furthermore, this study elucidated the specific mechanism of action of lipid metabolites on osteocytes, analyzed the relationship between lipid metabolism abnormalities and osteoporosis, and provided ideas for further clinical research on lipid metabolism-related osteoporosis.

Heart failure (HF) represents the terminal stage of multiple cardiovascular disorders and is characterized by substantial morbidity, disability, and mortality. Although standard pharmacotherapies offer partial symptomatic relief, their capacity to halt or reverse disease progression remains limited. In recent years, autophagy—an essential intracellular degradation and recycling process that safeguards cardiomyocyte homeostasis—has emerged as a critical determinant in the onset and progression of HF. In this review, we systematically examined approximately 170 research articles related to “natural compounds-autophagy-HF” published up to 2025, and synthesized major advances reported over the past five years. Based on chemical structure and natural source, representative bioactive compounds were categorized into five major classes: flavonoids, polyphenols, alkaloids, terpenoids, and marine-derived molecules. We then integrated evidence on the principal autophagy-regulatory signaling cascades influenced by these compounds, including the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) axis, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), sirtuin 1 (SIRT1)/forkhead box O (FOXO), BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/NIP3-like protein X (NIX), and Beclin-1 pathways. Moreover, this review summarizes how these natural compounds modulate autophagy to attenuate key pathological processes associated with HF, including cardiac hypertrophy, adverse ventricular remodeling, mitochondrial dysfunction, and cardiomyocyte apoptosis. By comparing convergent mechanisms and compound-specific differences in autophagy-mediated cardioprotection, we highlight emerging mechanistic patterns and therapeutic implications. Collectively, through structured classification of compounds, integration of autophagy signaling pathways, and assessment of translational potential, this review provides a systematic framework to guide the rational application and further development of natural products for the prevention and treatment of HF. Graphical abstract

BACKGROUND Autoimmune gastritis (AIG) is recognized endoscopically by the presence of antrum-sparing corpus-dominant atrophy, known as reverse atrophy. However, a past Helicobacter pylori (H. pylori ) infection can obscure this classic pattern. We present two cases of AIG with past H. pylori infection and highlight a novel endoscopic sign that may aid AIG recognition when typical features are absent. CASE SUMMARY One patient reported postprandial fullness, while the other was asymptomatic. Neither had a history of H. pylori eradication therapy. Both tested negative on a urea breath test and positive for anti-parietal cell antibodies. In both patients, endoscopy revealed mucosal atrophy involving both the corpus and antrum, which was counter to the characteristic reverse atrophy pattern typically seen in AIG. Beyond the atrophic border, we observed a distinct pattern of gyrus-like changes, manifesting as elevated mucosa between deep fissures. Histologically, targeted biopsies from these gyrus-like areas revealed parietal cell degeneration, lymphocytic infiltration, and hyperplasia of enterochromaffin-like cells, consistent with early histopathologic changes seen in AIG. These results supported diagnoses of AIG with past H. pylori infection. CONCLUSION Gyrus-like changes may serve as a novel endoscopic clue of AIG with past H. pylori infection.

Osteoporosis (OP) is a systemic degenerative skeletal disorder characterized by reduced bone mass and compromised biomechanical properties, with its pathogenesis closely associated with excessive osteoclast activation and dysregulated bone resorption. Emerging evidence has revealed that the osteoclast lysosomal–resorption apparatus (LRA) serves not only as the principal effector system responsible for bone matrix degradation but also as a critical hub governing the circadian regulation of bone resorption. Disruption of circadian rhythms can impair LRA homeostasis and function, thereby promoting osteoclast hyperactivity and accelerating pathological bone loss. In this review, we systematically summarize the mechanistic roles of the LRA in osteoclastic bone resorption and comprehensively discuss the multilayered regulatory network through which the circadian clock modulates LRA activity. Particular emphasis is placed on the pathological significance of circadian clock–LRA interactions in distinct forms of osteoporosis. Furthermore, we highlight emerging therapeutic strategies targeting circadian regulation and lysosomal homeostasis restoration as potential approaches for osteoporosis intervention. Elucidating the mechanistic basis of the circadian clock–LRA axis will not only advance our understanding of osteoporosis pathogenesis and progression but also provide a theoretical framework for chronopharmacology and rhythm-based therapeutic interventions. These insights may ultimately facilitate the development of more precise and personalized strategies for osteoporosis prevention, treatment, and long-term management.