Chronic Diseases and Translational Medicine最新文献

Calcium-sensing receptor (CaSR), a family C G-protein-coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca²⁺, Mg²⁺, amino acids (e.g., L-Trp and L-Phe), small peptides, anions (e.g., HCO₃⁻ and PO₄³⁻), and pH. CaSR-mediated intracellular Ca²⁺ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca²⁺-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.

Cytarabine is one of the most used drugs for the treatment of hematological malignancies such as leukemia and non-Hodgkin's lymphoma. In cells, cytarabine is activated into ara-CTP, which can replace deoxycytidine triphosphate (dCTP) and become incorporated into the DNA of proliferating cells. Thus, it can block DNA synthesis, resulting in proliferation arrest and cell death.¹ High doses of cytarabine usually induce dermatological toxicity commonly reported as morbilliform eruptions, acral erythema, neutrophilic eccrine hidradenitis, vasculitis, toxic epidermal necrolysis, and eccrine squamous syringome taplasia.^2-5 Of these toxicity effects, violaceous erythema is especially rare.^{6, 7} Herein, we present a case of delayed generalized violaceous erythema associated with cytarabine and discuss its necessary treatment.

An 11-year-old boy came to the hospital complaining of an ache in the lower limb. Bone marrow puncture results confirm that he has acute lymphoblastic leukemia. He received a chemotherapy with cyclophosphamide, cytarabine, and 6-mercaptopurine (according to the Chinese Children Cancer Group [CCCG]-Acute lymphoblastic leukemia [ALL]-2015) for induction chemotherapy. The treatment course lasted 7 days, with cytarabine (100 mg/m²) and 6-mercaptopurine (60 mg/m²) given daily. Cyclophosphamide (1 g/m²) was given on the first day. On the seventh day of chemotherapy, he developed a high fever (39.8°C). The next day, a florid, diffuse, nonpruritic erythematous macule eruption appeared on his face, ears, and scalp. Antihistamines have no effect on the erythematous macule. Over the next 24 h, erythematous macules spread over his neck, arms, chest, abdomen, and back (Figure 1A). The percentage of eosinophils (6%; reference value, 0–5%) increased transiently on the eighth day of chemotherapy. On the ninth day of chemotherapy, erythematous macules coalesced into purpuric plaques and spread throughout the body (Figure 1B). The color of the erythema turned to bright red as well as a growing facial edema was observed. Histopathological examination of skin biopsy tissue demonstrated neutrophilic, lymphocytic infiltration and erythrocytic extravasation (Figure 2). C-reactive protein (CRP) level (56.7 mg/L; reference value, 0–8 mg/L) and D-dimer (2860 µg/L; reference value, 0–550 µg/L) were high throughout the period of erythema. Meanwhile, anti-infective therapy showed no effect on the progression of erythema or the reduction of CRP. On the 12th day of initial cytarabine exposure, dry desquamation was noted (Figure 1C), with complaints of slight pruritus. Then, the eruption faded away and disappeared on the 17th day after initial exposure to cytarabine (Figure 1D). However, in the later stage of erythema, the patient developed a liver injury and lasted for 13 days. After 28 days of initial exposure to cytarabine, the patient recovered. Subs