Current Molecular Medicine - Volume 24, Issue 9, 2024

Rapid progress is being made in the area of nanotechnology; solid lipid nanoparticles are currently at the forefront of research and development. They have the capability of becoming employed in an extensive number of applications, including the delivery of medications, clinical treatment, and research, in addition to uses in other areas of academic inquiry that could benefit from their utilisation. This article presents a thorough analysis of solid lipid nanoparticles, covering subjects such as their goals, preparation strategy, applications, advantages, and possible remedies for the issues that have been raised. This review provides a discussion of solid lipids that is both in-depth and comprehensive. Studies that investigate the manner in which SLNs are prepared and the routes via which they are administered are typical. Aspects concerning the route of administration of SLNs as well as the destiny of the carriers in vivo are also investigated in this paper.

In this review we have brought forward various nuclear imaging modalities used in the diagnosis, staging, and management of thyroid cancer. Thyroid cancer is the most common endocrine malignancy, accounting for approximately 3% of all new cancer diagnoses. Nuclear imaging plays an important role in the evaluation of thyroid cancer, and the use of radioiodine imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the management of this disease. Radioiodine imaging involves the use of Iodine-123 [I-123] or Iodine-131 [I-131] to evaluate thyroid function and detect thyroid cancer. I-123 is a gamma-emitting isotope that is used in thyroid imaging to evaluate thyroid function and detect thyroid nodules. I-131 is a beta-emitting isotope that is used for the treatment of thyroid cancer. Radioiodine imaging is used to detect the presence of thyroid nodules and evaluate thyroid function. FDG imaging is a PET imaging modality that is used to evaluate the metabolic activity of thyroid cancer cells. FDG is a glucose analogue that is taken up by cells that are metabolically active, such as cancer cells. FDG PET/CT can detect primary thyroid cancer and metastatic disease, including lymph nodes and distant metastases. FDG PET/CT is also used to monitor treatment response and detect the recurrence of thyroid cancer. Somatostatin receptor imaging involves the use of radiolabeled somatostatin analogues to detect neuroendocrine tumors, including thyroid cancer. Radiolabeled somatostatin analogues, such as Indium-111 octreotide or Gallium-68 DOTATATE, are administered to the patient, and a gamma camera is used to detect areas of uptake. Somatostatin receptor imaging is highly sensitive and specific for the detection of metastatic thyroid cancer. A comprehensive search of relevant literature was done using online databases of PubMed, Embase, and Cochrane Library using the keywords "thyroid cancer," "nuclear imaging," "radioiodine imaging," "FDG PET/CT," and "somatostatin receptor imaging" to identify relevant studies to be included in this review. Nuclear imaging plays an important role in the diagnosis, staging, and management of thyroid cancer. The use of radioiodine imaging, thyroglobulin imaging, FDG imaging, and somatostatin receptor imaging are all valuable tools in the evaluation of thyroid cancer. With further research and development, nuclear imaging techniques have the potential to improve the diagnosis and management of thyroid cancer and other endocrine malignancies.

Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.

Nicotine, minodronic acid, nicotinamide (niacin), zolpidem, zolimidine, and other pyridine-based chemicals play vital roles in medicine and biology. Pyridinecontaining drugs are widely available on the market to treat a wide range of human ailments. As a result of these advances, pyridine research is continually expanding, and there are now higher expectations for how it may aid in the treatment of numerous ailments. This evaluation incorporates data acquired from sources, like PubMed, to provide a thorough summary of the approved drugs and bioactivity data for compounds containing pyridine. Most of the reactions discussed in this article will provide readers with a deeper understanding of various pyridine-related examples, which is necessary for the creation of copper catalysis-based synthetic processes that are more accessible, secure, environmentally friendly, and practical, and that also have higher accuracy and selectivity. This paper also discusses significant innovations in the multi-component copper-catalyzed synthesis of N-heterocycles (pyridine), with the aim of developing precise, cost-effective, and environmentally friendly oxygenation and oxidation synthetic methods for the future synthesis of additional novel pyridine base analogs. Therefore, the review article will serve as a novel platform for researchers investigating copperbased pyridine compounds.

The liver plays a critical role in metabolic processes, making it vulnerable to injury. Researchers often study carbon tetrachloride (CCl4)-induced hepatotoxicity in model organisms because it closely resembles human liver damage. This toxicity occurs due to the activation of various cytochromes, including CYP2E1, CYP2B1, CYP2B2, and possibly CYP3A, which produce the trichloromethyl radical (CCl3*). CCl3* can attach to biological molecules such as lipids, proteins, and nucleic acids, impairing lipid metabolism and leading to fatty degeneration. It can also combine with DNA to initiate hepatic carcinogenesis. When exposed to oxygen, CCl3* generates more reactive CCl3OO*, which leads to lipid peroxidation and membrane damage. At the molecular level, CCl4 induces the release of several inflammatory cytokines, including TNF-α and NO, which can either help or harm hepatotoxicity through cellular apoptosis. TGF-β contributes to fibrogenesis, while IL-6 and IL-10 aid in recovery by minimizing anti-apoptotic activity and directing cells toward regeneration. To prevent liver damage, different interventions can be employed, such as antioxidants, mitogenic agents, and the maintenance of calcium sequestration. Drugs that prevent CCl4- induced cytotoxicity and proliferation or enhance CYP450 activity may offer a protective response against hepatic carcinoma.

Tissue factor (TF) is an integral transmembrane protein associated with the extrinsic coagulation pathway. TF gene expression is regulated in response to inflammatory cytokines, bacterial lipopolysaccharides, and mechanical injuries. TF activity may be affected by phosphorylation of its cytoplasmic domain and alternative splicing. TF acts as the primary initiator of physiological hemostasis, which prevents local bleeding at the injury site. However, aberrant expression of TF, accompanied by the severity of diseases and infections under various pathological conditions, triggers multiple signaling pathways that support thrombosis, angiogenesis, inflammation, and metastasis. Protease-activated receptors (PARs) are central in the downstream signaling pathways of TF. In this study, we have reviewed the TF signaling pathways in different pathological conditions, such as wound injury, asthma, cardiovascular diseases (CVDs), viral infections, cancer and pathological angiogenesis. Angiogenic activities of TF are critical in the repair of wound injuries and aggressive behavior of tumors, which are mainly performed by the actions of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1 (HIF1-α). Pro-inflammatory effects of TF have been reported in asthma, CVDs and viral infections, including COVID-19, which result in tissue hypertrophy, inflammation, and thrombosis. TF-FVII induces angiogenesis via clotting-dependent and -independent mechanisms. Clottingdependent angiogenesis is induced via the generation of thrombin and cross-linked fibrin network, which facilitate vessel infiltration and also act as a reservoir for endothelial cells (ECs) growth factors. Expression of TF in tumor cells and ECs triggers clotting-independent angiogenesis through induction of VEGF, urokinase-type plasminogen activator (uPAR), early growth response 1 (EGR1), IL8, and cysteine-rich angiogenic inducer 61 (Cyr61).

Objective: To observe the short-term effect of sequentially combined multimodal artificial liver treatment (SCMALT) on HBV-related acute-on-chronic liver failure (HBV-ACLF). Methods: HBV-ACLF patients 155 cases undergoing artificial liver treatment were analyzed, and they were sorted into the SCMALT group and the conventional-modal artificial liver treatment (CALT) group. The clinical data of all patients were recorded and the serum levels of interleukin-8 (IL-8), chemokine interferon-inducible protein-10 (IP-10), and interleukin-6 (IL-6) were detected. The changes in the 30-day survival rate, cytokine level, model for end-stage liver disease (MELD) score, and complications of artificial liver treatment were analyzed. Results: After being followed up for 30 days, 104 patients survived and 51 died. At the end of the whole-course treatment, the decreases in IL-6, IP-10, and IL-8 levels and MELD scores in the SCMALT group were greater than in the CALT group. Cox regression suggested WBC (OR=1.066, 95% CI 1.012-1.123, P=0.017), AT-III activity (OR=0.935, 95% CI 0.907-0.964, p=0.000) at baseline, artificial liver treatment mode (OR=0.362, 95% CI 0.164-0.800, p=0.012), number of artificial liver treatments (OR=0.656, 95% CI 0.436-0.986, p=0.043), spontaneous peritonitis (OR=0.337, 95% CI 0.165-0.689, p=0.003), and hepatic encephalopathy (OR=0.104, 95% CI 0.028-0.388, p=0.001) were independent influencing factors of 30-day survival rate. SCMALT can significantly prolong the survival period of the patient. No obvious difference was shown in the proportions of bleeding and circulation instability between the two groups (p>0.05). Conclusion: Compared with the CALT, SCMALT can more effectively remove inflammatory mediators and reduce the MELD score in HBV-ACLF patients, which can obviously ameliorate the prognosis, with less effect on the platelet count.

Background: Despite recent progress in drug development, lung cancer remains a complex disease that poses a major public health issue worldwide, and new therapeutic strategies are urgently needed because of the failure of standard treatments. Ion channels play a critical role in various cellular processes that regulate cell proliferation, differentiation, and cell death. Objectives: The potential of ion channel modulators as tumor growth suppressors has been highlighted in recent studies. Therefore, we hypothesized that hydroquinidine (HQ), a previously understudied potassium channel modulator, might have anticarcinogenic activity against A549 cells. Methods: The anticancer potential of HQ was investigated using various wellestablished in vitro assays. Results: HQ significantly decreased colony formation and tumorigenicity and exhibited a significant anti-migratory effect in A549 cells. Our results demonstrated that HQ significantly inhibited the growth of cancer cells by decreasing the proliferation rate while increasing cell death. The altered gene expression profile in response to treatment with HQ was consistent with the observed cellular effects. Incubation of cells with HQ resulted in the downregulation of genes involved in cell division and survival, while genes promoting cell cycle arrest and apoptosis were upregulated. Conclusion: Our findings suggest that HQ has the potential to limit lung cancer growth as a novel potent anticarcinogenic agent. However, more investigations are needed to gain further insight into the mechanism of action of HQ and to evaluate its efficacy in in vivo models.

Introduction: The macrophage migration inhibitory factor (MIF) plays a pivotal role in the development of rheumatoid arthritis (RA). Previous research indicates that MIF can trigger the expression of cytokine profiles associated with Th1, Th2, and Th17 responses in peripheral blood mononuclear cells (PBMC) from both RA patients and control subjects (CS). Despite these, few studies to date precisely elucidate the molecular mechanisms involved. The present study aimed to associate the expression of Th differentiation TF (T-bet, GATA-3, RORγt) with MIF receptors (CD44, CD74, CXCR2, 4, 7) and Th1, Th2, and Th17 cytokines in PBMC from CS and RA patients. Method: PBMC from both groups was cultured for 24 h. The expression of the canonical and non-canonical MIF receptors and the TF was determined by flow cytometry. Additionally, multiplex bead analysis was employed to assess the levels of cytokines in the culture supernatants. The findings revealed that T CD4+ lymphocytes in the CS group exhibited a heightened expression of CD74 (p<0.05), whereas RA patients displayed an elevated expression of CXCR7 (p<0.001). Furthermore, T CD4+ lymphocytes from RA patients exhibited greater expression of GATA3, RORγt, and FOXP3, along with elevated levels of pro-inflammatory cytokines compared to the CS group (p<0.001). Result: These results indicate that CD74 is more prominently expressed in PBMC from the CS group, whereas CXCR7 is more expressed in PBMC from RA patients. Conclusion: We also noted an increased secretion of Th17 profile cytokines in RA, potentially influenced by the activation of FOXP3 via CD74 and RORγt through CXCR7 using the endocytic pathway.

Objective: To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. Methods: In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. Results: When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. Conclusion: CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.