Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective: To examine the effect of intracellular vesicles (IVs) and extracellular vesicles (EVs) that originated from periodontal ligament stem cells (PDLSCs) on the osteogenic differentiation of PDLSCs within a lipopolysaccharide (LPS)-simulated inflammatory microenvironment, and to provide new insights for the application of IVs in the repair and regeneration of periodontal tissue in periodontitis. Methods: Ethical approval was obtained from the institution. Human-origin PDLSCs were extracted, and the IVs and EVs from PDLSCs at the 3rd-6th passages were gathered and identified using transmission electron microscopy, nano flow cytometry (Nano FCM) analysis, and Western Blot. The 3rd-6th generations of PDLSCs were categorized into the following groups: Control group, LPS group, LPS + 100 μg/mL EVs group (LPS+EVs group), and LPS + 100 μg/mL IVs group (LPS+IVs group). The effects of the IVs and EVs on the anti-inflammatory and osteogenic differentiation of PDLSCs in an inflammatory microenvironment were assessed by using a Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), Western Blot, alkaline phosphatase (ALP) staining, and alizarin red staining (ARS). Results: Under transmission electron microscopy, the IVs and EVs derived from PDLSCs displayed a double-layer membrane structure. NanoFCM analysis revealed that the average diameters of the IVs and EVs were 79.6 nm and 82.1 nm, respectively. Western Blot analysis indicated that the surface proteins CD9, CD63, and CD81 of the IVs and EVs were positively expressed, while calnexin was negatively expressed, indicating that IVs and EVs were successfully obtained. Compared with the Control group, the proliferation of PDLSCs in the LPS group was reduced, while the levels of inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the cell supernatant were increased, the mRNA expressions of osteogenic differentiation-related genes, including osteoblast-related genes runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN) of PDLSCs were reduced, the protein expressions of RUNX2 and osteopontin (OPN) were also decreased (P<0.05); compared with the LPS group, the proliferation of PDLSCs in the LPS+EVs group and LPS+IVs group were significantly increased, while the levels of IL-6, TNF-α were significantly reduced, and the mRNA expressions of RUNX2, ALP, OCN were significantly increased, the protein expressions of RUNX2 and OPN were also significantly increased (P<0.05). Further, in the inflammatory microenvironment, Compared with EVs, IVs more significantly promote the proliferation of PDLSCs, inhibit TNF-α expression, enhance the expression of RUNX2 mRNA, upregulate the expression of RUNX2 and OPN proteins, increase ALP activity, and promote the formation of mineralized nodules (P<0.05). Conclusion IVs and EVs derived from PDLSCs can boost the proliferation of PDLSCs in an inflammatory microenvironment, inhibit the expression of inflammatory factors, and advance the osteogenic differentiation of PDLSCs. The anti-inflammatory and osteogenic effects of IVs are superior to those of EVs.

OBJECTIVE To offer a reference for the treatment of Mycobacterium iranicum infection by analyzing the diagnosis and management of a single case alongside literature-reported cases. METHODS Through case report and literature reviews， this study synthesized the clinical features， therapeutic regimens， and patient outcomes of those infected with M. iranicum. RESULTS In the single case documented in this report， subsequent to clinical pharmacists’ involvement in the consultation， the patient was prescribed a therapeutic regimen comprising levofloxacin （0.5 g， qd， ivgtt）+Clarithromycin sustained-release tablets （1 000 mg， qd， po） + Ethambutol tablets （0.75 g， qd， po）. The patient exhibited clinical improvement and was discharged after treatment. This article integrated 12 published studies， encompassing 13 patients （7 male and 6 female）， of whom 69.23% were aged ≥50 years. Patients infected with M. iranicum exhibited non-specific clinical manifestations and imaging features， with pulmonary infection as the primary presentation. Antimicrobial susceptibility test revealed that M. iranicum was susceptible to multiple agents， including amikacin， clarithromycin， linezolid， and ethambutol. The three-drug combination therapy was the most frequently employed regimen. In terms of clinical outcomes， there were 9 cases （69.23%） of clinical cure， 3 cases （23.08%） of bacteriological negativity conversion， and 1 case （7.69%） of treatment failure. CONCLUSIONS For M. iranicum infection， a triple-drug therapeutic regimen consisting of three agents with distinct mechanisms of action selected from amikacin， clarithromycin， moxifloxacin， levofloxacin， minocycline， ethambutol， and other relevant drugs may represent a relatively optimal strategy.

ObjectiveTo investigate the association between estimated glucose disposal rate （eGDR） and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients （mean age： 62（53-68） years） who underwent coronary angiography for suspected coronary artery disease （53.9% were male）. Insulin resistance level （IR） was calculated according to eGDR formula： eGDR = 21.158 - （0.09 × WC） - （3.407 × hypertension） - （0.551 × HbA1c） ［hypertension （yes = 1 / no = 0）， HbA1c = HbA1c （%）］. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels： no-obstructive CAD group （all coronary stenosis were<50%， n=704）， Single-vessel CAD group （only one involved major coronary artery stenosis≥50%， n=205）， Multi-vessel CAD group （two or more involved major coronary arteries stenosis≥50%， n=349）； Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic （ROC） curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. In multivariate logistic regression models， individuals with the lowest quantile of eGDR （T1） were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR （T3） （OR： 2.79； 95%CI： 1.72~4.55； P<0.001）. Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD （P-nonlinear>0.05）. In non-diabetic patients， compared with the reference group （T3）， the T1 group had a significantly increased risk of CAD （OR： 1.42； 95% CI： 1.00~2.01； P<0.05） and multi-vessel CAD （OR： 1.86； 95%CI： 1.21~2.86； P<0.05）. No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis， when eGDR was added to traditional model for CAD， significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR， as a non-insulin measure to assess IR， could be a valuable indicator of CAD severity for population.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.
Calcium ; Acupuncture Therapy ; Acupuncture ; Acupuncture Analgesia/methods* ; Acupuncture Points ; Technology

Chemotherapy-induced complications, particularly lethal cardiovascular diseases, pose significant challenges for cancer survivors. The intertwined adverse effects, brought by cancer and its complication, further complicate anticancer therapy and lead to diminished clinical outcomes. Simple supplementation of cardioprotective agents falls short in addressing these challenges. Developing bi-functional co-therapy agents provided another potential solution to consolidate the chemotherapy and reduce cardiac events simultaneously. Drug repurposing was naturally endowed with co-therapeutic potential of two indications, implying a unique chance in the development of bi-functional agents. Herein, we further proposed a novel "trilogy of drug repurposing" strategy that comprises function-based, target-focused, and scaffold-driven repurposing approaches, aiming to systematically elucidate the advantages of repurposed drugs in rationally developing bi-functional agent. Through function-based repurposing, a cardioprotective agent, carvedilol (CAR), was identified as a potential neddylation inhibitor to suppress lung cancer growth. Employing target-focused SAR studies and scaffold-driven drug design, we synthesized 44 CAR derivatives to achieve a balance between anticancer and cardioprotection. Remarkably, optimal derivative 43 displayed promising bi-functional effects, especially in various self-established heart failure mice models with and without tumor-bearing. Collectively, the present study validated the practicability of the "trilogy of drug repurposing" strategy in the development of bi-functional co-therapy agents.

This paper explains the mechanism of the mutual switching between physiological sleep and wakefulness from the aspects of the sleep circadian system and the sleep homeostasis system. In the circadian rhythm system, with the suprachiasmatic nucleus as the core, the anatomical connections between the suprachiasmatic nucleusand various systems that affect sleep are summarized, starting from the suprachiasmatic nucleus, passing through the four pathways of the melatonin system, namely, subventricular area of the hypothalamus, the ventrolateral nucleus of the preoptic area, orexin neurons, and melatonin, then the related mechanisms of their regulation of sleep and wakefulness are expounded. In the sleep homeostasis system, with adenosine and prostaglandin D2 as targets, the role of hypnogen in sleep arousal mechanisms in regulation is also expounded.

Glucagon-like peptide-1 ( GLP-1 ) is secreted by gut enteroendocrine cells. GLP-1 receptor agonists ( GLP-1 RAs) control glucose-related augmentation of insulin and suppress glu-cagon secretion. GLP-lRAs also inhibit gastric emptying, food intake and limit weight gain. In the past decade, significant progresses have been made in the investigation on the effects of GLP-1 RAs on cardiovascular system. The potential advantages of oral small-molecule GLP-1 RAs could improve the application of this class of drugs. This review highlights the multiple cardiovascular profiles of GLP-1 RAs in the treatment of cardiovascular diseases to provide new insights into cardiovascular benefits of GLP-1 RAs.

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.