Octa-Arginine-Conjugated Liposomal Nimodipine Incorporated in a Temperature-Responsive Gel for Nasoencephalic Delivery.

Nimodipine is the primary clinical drug used to treat cerebral vasospasm following subarachnoid hemorrhage. Currently, tablets have low bioavailability when taken orally, and injections contain ethanol. Therefore, we investigated a new method of nimodipine administration, namely, nasoencephalic administration. Nasal administration of nimodipine was carried out by attaching the cell-penetrating peptide octa-arginine (R8) to liposomes of nimodipine and incorporating it into a temperature-sensitive in situ gel. The prepared liposomes and gels underwent separate evaluations for in vitro characterization. In vitro release exhibited a significant slow-release effect. In vitro toad maxillary cilia model, RPMI 2650 cytotoxicity, and in vivo SD rat pathological histotoxicity experiments showed that all the dosage from the groups had no significant toxicity to toad maxillary cilia, RPMI 2650 cells, and SD rat tissues and organs, and the cilia continued to oscillate up to 694 ± 10.15 min, with the survival rate of the cells being above 85%. A transwell nasal mucosa cell model and an isolated porcine nasal mucosa model were established, and the results showed that the osmolality of the R8-modified nimodipine liposomal gel to nasal mucosal cells and isolated porcine nasal mucosa was 30.41 ± 2.14 and 65.9 ± 7.34 µg/mL, respectively, which was significantly higher than that of the NM-Solution and PEGylated nimodipine liposome gel groups. Animal fluorescence imaging studies revealed that the R8-modified nimodipine liposomal gel displayed increased brain fluorescence intensity compared to the normal liposomal gel. Pharmacokinetic results showed that after transnasal administration, the AUC(0-∞) of the R8-modified nimodipine liposomal gel was 11.662 ± 1.97 µg·mL-1, which was significantly higher than that of the plain nimodipine liposomal gel (5.499 ± 2.89 µg·mL-1). Brain-targeting experiments showed that the brain-targeting efficiencies of the PEGylated nimodipine liposome gel and R8-modified PEGylated nimodipine liposome gels were 20.44 and 33.45, respectively, suggesting that R8/PEG/Lip-NM-TSG significantly increased the brain-targeting of the drug.

Cancer Antibody Engineering: Comparison of Mammalian, Yeast, Bacterial, Plants, Cell-free and Hybridoma Expression Systems.

BACKGROUND: Cancer is a significant issue worldwide. Generally, commercially available treatments, such as surgery, radiotherapy, and chemotherapy, are associated with undesirable complications. Hence, immunotherapy serves as a crucial alternative to those treatment options. OBJECTIVE: This modality is aimed to boost the immune system through the application of engineered antibodies, which can be produced using recombinant DNA technology. RESULTS: The discussion of the technologies leads to an introduction of the single-chain variable fragment (scFv). Thereafter, the advantages, disadvantages, and challenges associated with different expression systems, such as mammalian cells, yeast cells, bacterial cells, plant cells, and phage display were discussed comprehensively. CONCLUSION: Furthermore, conventional approaches such as hybridoma and modern approaches such as cell-free protein synthesis (CFPS) and simple colony assays are included. In short, this article has compiled evidence relating to each display system and may serve as a reference for those who aim to explore antibody engineering using one of the methods listed in this article.

Prevention of Parkinson's disease: from risk factors to early interventions.

Parkinson's disease (PD) is a debilitating neurological disorder characterized by progressively worsening motor dysfunction. Currently, available therapies merely alleviate symptoms, and there are no cures. Consequently, some researchers have now shifted their attention to identifying the modifiable risk factors of PD, with the intention of possibly implementing early interventions to prevent the development of PD. Four primary risk factors for PD are discussed including environmental factors (pesticides and heavy metals), lifestyle (physical activity and dietary intake), drug abuse, and individual comorbidities. Additionally, clinical biomarkers, neuroimaging, biochemical biomarkers, and genetic biomarkers could also help to detect prodromal PD. This review compiled available evidence that illustrates the relationship between modifiable risk factors, biomarkers, and PD. In summary, we raise the distinct possibility of preventing PD via early interventions of the modifiable risk factors and early diagnosis.

pH-Responsive and Mucoadhesive Nanoparticles for Enhanced Oral Insulin Delivery: The Effect of Hyaluronic Acid with Different Molecular Weights.

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA-PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA-PDM-INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA-PDM-INS, M-HA-PDM-INS, H-HA-PDM-INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA-PDM-INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA-PDM-INS was investigated. The release of INS from H-HA-PDM-INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA-PDM-INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA-PDM-INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA-PDM-INS, regardless of the MW of HA, was demonstrated using CCK-8 and live-dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA-PDM-INS, M-HA-PDM-INS, and H-HA-PDM-INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA-PDM-INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.

Synthesis and Antibacterial Activity Evaluation of Imidazole Derivatives Containing 6-Methylpyridine Moiety.

A series of 2-cyclopropyl-5-(5-(6-methylpyridin-2-yl)-2-substituted-1H-imidazol-4-yl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazoles (15a-t and 16a-f) were synthesized and their antibacterial activities were evaluated. More than half of the compounds showed moderate or strong antibacterial activity. Among them, compounds 15t (MIC=1-2 µg/mL) and 16d (MIC=0.5 µg/mL) showed the strongest antibacterial activities. Notably, compound 16d did not exhibit cytotoxicity in HepG2 cells and did not show hemolysis like the positive control compound Gatifloxacin. The results suggest that compound 16d should be further investigated as a candidate antibacterial agent.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Application of plasma SARS-CoV-2 quantitative antigen detection in the diagnosis and treatment of COVID-19 / 中华预防医学杂志

The corona virus disease 2019(COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has created an urgent need of scientific and effective biomarkers for the purpose of prevention and control. Currently, commonly employed viral nucleic acids, antibodies, and rapid antigen test detection technologies all exhibit a range of limitations, including restricted applicability, inadequate sensitivity and specificity. Plasma SARS-CoV-2 quantitative antigen, as an emerging biomarker, has garnered significant attention due to its potential clinical value in the diagnosis and management of COVID-19. This article comprehensively analyzes the principles and clinical applications of quantitative detection technology for plasma SARS-CoV-2 antigen. Additionally, it explores the challenges encountered in this field and provides insights into future prospects.

Application of plasma SARS-CoV-2 quantitative antigen detection in the diagnosis and treatment of COVID-19 / 中华预防医学杂志

The corona virus disease 2019(COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has created an urgent need of scientific and effective biomarkers for the purpose of prevention and control. Currently, commonly employed viral nucleic acids, antibodies, and rapid antigen test detection technologies all exhibit a range of limitations, including restricted applicability, inadequate sensitivity and specificity. Plasma SARS-CoV-2 quantitative antigen, as an emerging biomarker, has garnered significant attention due to its potential clinical value in the diagnosis and management of COVID-19. This article comprehensively analyzes the principles and clinical applications of quantitative detection technology for plasma SARS-CoV-2 antigen. Additionally, it explores the challenges encountered in this field and provides insights into future prospects.

Preparation of Betulinic Acid Galactosylated Chitosan Nanoparticles and Their Effect on Liver Fibrosis.

Aim: Liver fibrosis is mainly characterized by the formation of fibrous scars. Galactosylated chitosan (GC) has gained increasing attention as a liver-targeted drug carrier in recent years. The present study aimed to investigate the availability of betulinic acid-loaded GC nanoparticles (BA-GC-NPs) for liver protection. Covalently-conjugated galactose, recognized by asialoglycoprotein receptors exclusively expressed in hepatocytes, was employed to target the liver. Materials and Methods: Galactose was coupled to chitosan by chemical covalent binding. BA-GC-NPs were synthesized by wrapping BA into NPs via ion-crosslinking method. The potential advantage of BA-GC-NP as a liver-targeting agent in the treatment of liver fibrosis has been demonstrated in vivo and in vitro. Results: BA-GC-NPs with diameters <200 nm were manufactured in a virtually spherical core-shell arrangement, and BA was released consistently and continuously for 96 h, as assessed by an in vitro release assay. According to the safety evaluation, BA-GC-NPs demonstrated good biocompatibility at the cellular level and did not generate any inflammatory reaction in mice. Importantly, BA-GC-NPs showed an inherent liver-targeting potential in the uptake behavioral studies in cells and bioimaging tests in vivo. Efficacy tests revealed that administering BA-GC-NPs in a mouse model of liver fibrosis reduced the degree of liver injury in mice. Conclusion: The findings showed that BA-GC-NPs form a safe and effective anti-hepatic fibrosis medication delivery strategy.

Vitamin A - modified Betulin polymer micelles with hepatic targeting capability for hepatic fibrosis protection.

Targeting hepatic stellate cells (HSCs) can improve the therapeutic efficacy of medicines used to treat hepatic fibrosis. The present work aimed to study the feasibility of homing devices with vitamin A(VA) chemically attached for delivering betulin(Bt)specifically to HSCs. The manufacture and characterisation of VA modified poly (ethylene glycol) -poly (lactide-co-glycolide) block copolymer micelles loaded with Bt (Bt/ VAPPMs) and their potential therapeutic benefits in vitro and in vivo are described in this paper. Bt/VAPPMs were made in a nearly spherical core-shell configuration with diameters under 200nm.In vitro release study showed that Bt/VAPPMs exhibited steady and continuous release for over 168 hours. Bt/VAPPMs had good biocompatibility at the cellular level, according to the safety evaluation, and elicited no inflammatory response in mice. More importantly, as uptake behavior studied in cells and bioimaging experiments in vivo, Bt/VAPPMs exhibited an instinctive liver- targeting capability to focus on activated HSCs. Efficacy tests revealed that administering Bt/VAPPMs effectively inhibits collagen I expression in LX-2 cells in vitro, and this effect was also seen in a mouse model of liver fibrosis. Overall, results demonstrated that Bt/VAPPMs is a promising drug delivery system that possesses specific HSCs targeting ability for treating hepatic fibrosis.

Importance of cerebrospinal fluid in the diagnosis and treatment of central nervous system diseases / 中华检验医学杂志

Cerebrospinal fluid (CSF) is a colorless and transparent fluid filling the ventricular system, subarachnoid space, and central canal of the spinal cord, which could directly reflect diseases from the human central nervous system. As advanced technologies were used widely in CSF-based tests, they provided a new perspective for diagnosing, prognosis and treatment monitoring of central nervous system diseases based on CSF. The main challenges currently are resolving the biological variation of CSF markers, selecting appropriate technologies, and standardizing CSF-based analysis.

Preliminary application experience of disk microfluidic chip for detecting CALR gene mutation in patients with cerebral infarction / 中华检验医学杂志

Objective:To establish a disk (CD) microfluidic chip detection platform for the rapid detection of CALR-1 and CALR-2 mutations in patients with cerebral infarction, and summarize its clinical application value.Methods:Based on microfluidic technology and loop mediated isothermal amplification technology, a CD microfluidic chip detection platform for simultaneous detection of CALR-1 and CALR-2 gene mutations were established, and the sensitivity, specificity, repeatability and accuracy of the platform were verified. A total of 124 patients with cerebral infarction treated in Huashan Hospital, Shanghai Medical College, Fudan University from November 2019 to March 2021 were prospectively selected into the experimental group; and 80 healthy subjects were included in the control group. The CALR-1 and CALR-2 gene mutations in anticoagulant peripheral blood samples were detected by the CD microfluidic chip. Each chip could detect 4 samples at the same time and synchronously detect 3 indexes of each sample. The detection results could be obtained after isothermal amplification for 40 min. At the same time, sequencing method was used to verify the test results, and the consistency of the results of the two detection methods was compared.Results:Using this CD microfluidic chip platform, the synchronous amplification of 3 indexes in the sample could be completed within 40 min without the need of thermal circulation, and the whole detection process of the sample could be completed within 60 min. For samples with a high concentration of target nucleic acid, typical positive signals could be visualized after amplification for 10 min, and the test results would be available within 30 minutes after receiving the samples. The detection sensitivity of CD microfluidic chip method for CALR-1 and CALR-2 mutation load concentration was 1.0% and 0.5% respectively. Nonspecific amplification was not observed for the non-target nucleic acid samples, indicating the high specificity of this method. The coincidence rates of intra and inter batch repeatability were 100% (20/20) respectively. Two samples with CALR gene mutation were found in the cerebral infarction group, both of which were CALR-1 mutations (L367fs*46). There was no CALR-1 or CALR-2 mutation in the control group. The detection results of CD microfluidic chip method were completely consistent with the sequencing verification results (100% [204/204]).Conclusions:The CD microfluidic chip method could be used for the detection of CALR-1 and CALR-2 gene mutations in clinical samples of patients with cerebral infarction. This method has the advantages of high detection sensitivity, good detection specificity, fast detection speed and high detection flux, which is helpful to clarify the etiology of patients with cerebral infarction.

Prognostic effect of MyD88L265P gene mutation in cerebrospinal fluid in primary central nervous system lymphoma / 中华检验医学杂志

Objective:This study has investigated the value of detecting cerebrospinal fluid (CSF) MyD88L265P mutation and interleukin-10 (IL-10) levels in the prognosis of PCNSL.Methods:We retrospectively analyzed the clinical data, CSF characteristics (including cytology, cell counting, total protein, and the level of cytokine IL-10) and treatment process of 39 PCNSL patients newly diagnosed by surgery and pathology (18 males and 21 females, aged 40-73 years) from August 2013 to December 2016 in Hua Shan Hospital North. MyD88L265P mutation was detected by digital PCR in 39 paraffin-embedded tissues and 35 cerebrospinal fluid samples. Log-rank test was used for univariate analysis and Cox regression for multivariate analysis to establish the prognosis model of PCNSL which might be related to PCNSL first progress-free survival (PFS) and overall survival (OS).Results:The median age of the 39 PCNSL patients was 59 years old, with 30.8% (12/39) intraocular involvement. The mutation rate of MyD88L265P in tissues and cerebrospinal fluid was 74.4% (29/39) and 40.0% (14/35), respectively. 51.9% (14/27) patients were observed with MyD88L265P mutation in both tissues and CFS. Univariate analysis showed that intraocular involvement, high level of IL-10 in CFS (≥45 pg/ml), and MyD88L265P mutation in CFS are factors significantly influencing median progression-free survival (mPFS) of patients ( P<0.05). Patients with intraocular involvement had shorter OS than those without involvement which was statistically significant ( HR=6.5,95% CI 1.7-47.3, P<0.05). And multivariate analysis showed that intraocular involvement ( HR=2.4, 95% CI 1.3-7.8, P<0.05) and CFS MyD88L265P mutation ( HR=2.1, 95% CI 1.1-5.7, P<0.05) were independent prognostic factors for PFS. Conclusion:The presence of intraocular involvement and MyD88L265P mutation in CFS indicated poor prognosis of PCNSL patients. High CSF IL-10 level was not an independent factor affecting prognosis.

OCT parameters as a predictor of the efficacy of Ranibizumab in the treatment of macular edema secondary to central retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To analyze the correlation between optical coherence tomography(OCT)parameters and central retinal vein occlusion of macular edema secondary(CRVO-ME), and compare the clinical efficacy of ranibizumab combined with laser photocoagulation and ranibizumab alone in the treatment of CRVO-ME.METHODS:There were 43 case with 43 eyes of patients in CRVO-ME diagnosed in our hospital from January 2020 to December 2020 included in the present study and divided into two groups, namely A and B. Patients in group A were treated with ranibizumab combined with laser photocoagulation, while patients in group B were treated with ranibizumab alone. The structure of outer retina and “SAVE” scores were observed and estimated using OCT and fluorescein angiography(FFA)examination before and after the treatment at 1, 3, 6, 12mo, and then analyzed their correlation with best corrected visual acuity(BCVA, LogMAR). The BCVA, central macular thickness(CMT), intraocular pressure and average number of drug injections were also compared between the two groups before and after treatment.RESULTS:At 12mo after treatment, the BCVA in the OCT baseline external limiting membrane(ELM)intact group and baseline ellipsoid zone(EZ)intact group before and after treatment were significantly improved than those of the fracture group(0.47±0.16 vs 0.21±0.15, P=0.013; 0.44±0.20 vs 0.25±0.17, P=0.008). There was no statistically significant difference in BCVA changes between baseline RPE fracture group and RPE intact group(P>0.05). The number of patients with “S” and “A” at 1 score decreased significantly at 12mo after treatment in both groups, the BCVA of patients with “V” and “E” at 0 score before treatment was significantly improved than those patients at 1 score(all P<0.05). The BCVA and CMT of patients after treatment in groups A and B were both significant improved compared with before treatment(P<0.05). There were no significant differences in the BCVA and CMT in the number of drug injections between the two groups(P>0.05). In addition, there were no severe complications such as secondary glaucoma and endophthalmitis in both groups.CONCLUSION: Baseline status of ELM and EZ, presence or absence of vitreoretinal abnormalities(V), and focal leakage(E)could suggest the treatment efficacy of CRVO-ME. Ranibizumab in the treatment of CRVO-ME demonstrates prominent efficacy and great safety, and there was no better effect was observed when combined with laser photocoagulation.

Pathogenic spectrum and laboratory indicators of fungal infections in the central nervous system / 中华预防医学杂志

Central nervous system (CNS) fungal infections are challenging and difficult to diagnose and treat. This article introduces the high risk factors, pathogen spectrum and laboratory indicators that cause CNS fungal infection. As patients with CNS fungal infections are often accompanied by immunodeficiency, it is especially necessary for clinical early detection, early prevention, and early diagnosis, and timely and effective implementation of optimized diagnosis and treatment programs to prevent further deterioration of the disease.

Strategies of endovascular recanalization in acute vertebrobasilar artery occlusion of different lesion sites: a comparative analysis / 中华神经医学杂志

Objective:To investigate the pathogenesis, selection of endovascular treatment (EVT) strategies, and efficacies of acute vertebrobasilar artery occlusion (AVBAO) of different lesion sites.Methods:One hundred and five patients with AVBAO, admitted to and accepted EVT in our hospital from February 2017 to September 2019, were chosen in our study. The data of disease onset, imaging findings, EVT status, perioperative complications, and prognoses of these patients were collected. According to DSA results, the involved lesions were divided into 4 sites: the upper segment of basilar artery (BA), the middle segment of BA, the lower segment of BA, and the intracranial segment of vertebral artery (V4 segment), and patients with tandem lesions would be recorded as distal lesions. The risk factors, EVT strategies, and prognoses 90 d after follow-up (modified Rankin scale [mRS] scores≤3: good prognosis) were compared in patients with 4 different lesion sites.Results:There were significant differences in etiological classifications and percentage of patients combined with atrial fibrillation among patients with 4 different lesion sites ( P<0.05). There was significant difference in proportion of patients accepted emergency stent implantation among patients with 4 different lesion sites ( P<0.05): those with lesions at the V4 segment had the highest proportion of patients accepted emergency stent implantation (79.55%), followed by those with lesions at the lower segment of BA (50.00%). There was significant difference in EVT time (the time from arterial puncture to successful recanalization of occluded vessels) among patients with 4 different lesion sites ( P<0.05): the EVT time in patients with lesions at the middle segment of BA was the shortest (87.5 [58.5, 130.8] min), and the EVT time in patients with lesions at the lower segment of BA was the longest (115.0 [81.0, 163.0] min). There was no statistical difference among patients with different lesion sites in good prognosis rate 90 d after follow-up ( P>0.05). Conclusion:The pathogenesis of patients with different AVBAO lesion sites is different, so different EVT strategies should be adopted.

Edible Bird's Nest: Recent Updates and Industry Insights Based On Laboratory Findings.

Edible bird's nest (EBN) is a traditional Chinese delicacy made of the saliva of swiftlets found in Southeast Asia. With increasing demands for EBN, quality control of EBN products is important for safe consumption. The processing steps are particularly important for efficient extraction of bioactive compounds. Geographical location, collection place, and harvesting season contribute to differences in nutritional contents in EBN. Concerns regarding presence of adulterant, chemical, and microbial contaminants in EBN as well as authentication and chemical composition measuring methods are discussed in this review. Recent discoveries of beneficial health functions of EBN in antimicrobial and antiviral actions, immunomodulation, cancer prevention and treatment, tissue regeneration, cardiometabolic maintenance, antioxidant action and neuroprotection are also reviewed. Our review provides an update on the recent research on EBN.

Melatonin Induces Autophagy via Reactive Oxygen Species-Mediated Endoplasmic Reticulum Stress Pathway in Colorectal Cancer Cells.

Even though an increasing number of anticancer treatments have been discovered, the mortality rates of colorectal cancer (CRC) have still been high in the past few years. It has been discovered that melatonin has pro-apoptotic properties and counteracts inflammation, proliferation, angiogenesis, cell invasion, and cell migration. In previous studies, melatonin has been shown to have an anticancer effect in multiple tumors, including CRC, but the underlying mechanisms of melatonin action on CRC have not been fully explored. Thus, in this study, we investigated the role of autophagy pathways in CRC cells treated with melatonin. In vitro CRC cell models, HT-29, SW48, and Caco-2, were treated with melatonin. CRC cell death, oxidative stress, and autophagic vacuoles formation were induced by melatonin in a dose-dependent manner. Several autophagy pathways were examined, including the endoplasmic reticulum (ER) stress, 5'-adenosine monophosphate-activated protein kinase (AMPK), phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (Akt), and mammalian target of rapamycin (mTOR) signaling pathways. Our results showed that melatonin significantly induced autophagy via the ER stress pathway in CRC cells. In conclusion, melatonin demonstrated a potential as an anticancer drug for CRC.

Potential role of melatonin in prevention and treatment of leukaemia.

Leukaemia is a haematological malignancy originated from the bone marrow. Studies have shown that shift work could disrupt the melatonin secretion and eventually increase leukaemia incidence risk. Melatonin, a pineal hormone, has shown promising oncostatic properties on a wide range of cancers, including leukaemia. We first reviewed the relationship between shift work and the incidence rate of leukaemia and then discussed the role of melatonin receptors (MT1 and MT2) and their functions in leukaemia. Moreover, the connection between inflammation and leukaemia, and melatonin-induced anti-leukaemia mechanisms including anti-proliferation, apoptosis induction and immunomodulation are comprehensively discussed. Apart from that, the synergistic effects of melatonin with other anticancer compounds are also included. In short, this review article has compiled the evidence of anti-leukaemia properties displayed by melatonin and discuss its potential to act as adjunct for anti-leukaemia treatment. This review may serve as a reference for future studies or experimental research to explore the possibility of melatonin serving as a novel therapeutic agent for leukaemia.

Application of single cell sequencing technology in the cell analysis of cerebrospinal fluid / 中华检验医学杂志

The analysis of cerebrospinal fluid (CSF) facilitates the diagnosis and therapy of central nervous system (CNS) diseases. Compared to traditional methods, single-cell sequencing is conducive to analyze the cells composition and heterogeneity and discover scarce cells in CSF. Recent studies of single-cell sequencing in CSF has mainly focused on the neuroinfectious diseases, neurodegenerative and neuroinflammatory diseases, and leptomeningeal metastases (LM), reflecting the superiority and clinical value of single-cell sequencing in CNS diseases and providing new directions for the diagnosis and treatment of CNS diseases.