1.Applications of Vaterite in Drug Loading and Controlled Release
Xiao-Hui SONG ; Ming-Yu PAN ; Jian-Feng XU ; Zheng-Yu HUANG ; Qing PAN ; Qing-Ning LI
Progress in Biochemistry and Biophysics 2025;52(1):162-181
Currently, the drug delivery system (DDS) based on nanomaterials has become a hot interdisciplinary research topic. One of the core issues is drug loading and controlled release, in which the key lever is carriers. Vaterite, as an inorganic porous nano-material, is one metastable structure of calcium carbonate, full of micro or nano porous. Recently, vaterite has attracted more and more attention, due to its significant advantages, such as rich resources, easy preparations, low cost, simple loading procedures, good biocompatibility and many other good points. Vaterite, gained from suitable preparation strategies, can not only possess the good drug carrying performance, like high loading capacity and stable loading efficiency, but also improve the drug release ability, showing the better drug delivery effects, such as targeting release, pH sensitive release, photothermal controlled release, magnetic assistant release, optothermal controlled release. At the same time, the vaterite carriers, with good safety itself, can protect proteins, enzymes, or other drugs from degradation or inactivation, help imaging or visualization with loading fluorescent drugs in vitro and in vivo, and play synergistic effects with other therapy approaches, like photodynamic therapy, sonodynamic therapy, and thermochemotherapy. Latterly, some renewed reports in drug loading and controlled release have led to their widespread applications in diverse fields, from cell level to clinical studies. This review introduces the basic characteristics of vaterite and briefly summarizes its research history, followed by synthesis strategies. We subsequently highlight recent developments in drug loading and controlled release, with an emphasis on the advantages, quantity capacity, and comparations. Furthermore, new opportunities for using vaterite in cell level and animal level are detailed. Finally, the possible problems and development trends are discussed.
2.Acute Inflammatory Pain Induces Sex-different Brain Alpha Activity in Anesthetized Rats Through Optically Pumped Magnetometer Magnetoencephalography
Meng-Meng MIAO ; Yu-Xuan REN ; Wen-Wei WU ; Yu ZHANG ; Chen PAN ; Xiang-Hong LIN ; Hui-Dan LIN ; Xiao-Wei CHEN
Progress in Biochemistry and Biophysics 2025;52(1):244-257
ObjectiveMagnetoencephalography (MEG), a non-invasive neuroimaging technique, meticulously captures the magnetic fields emanating from brain electrical activity. Compared with MEG based on superconducting quantum interference devices (SQUID), MEG based on optically pump magnetometer (OPM) has the advantages of higher sensitivity, better spatial resolution and lower cost. However, most of the current studies are clinical studies, and there is a lack of animal studies on MEG based on OPM technology. Pain, a multifaceted sensory and emotional phenomenon, induces intricate alterations in brain activity, exhibiting notable sex differences. Despite clinical revelations of pain-related neuronal activity through MEG, specific properties remain elusive, and comprehensive laboratory studies on pain-associated brain activity alterations are lacking. The aim of this study was to investigate the effects of inflammatory pain (induced by Complete Freund’s Adjuvant (CFA)) on brain activity in a rat model using the MEG technique, to analysis changes in brain activity during pain perception, and to explore sex differences in pain-related MEG signaling. MethodsThis study utilized adult male and female Sprague-Dawley rats. Inflammatory pain was induced via intraplantar injection of CFA (100 μl, 50% in saline) in the left hind paw, with control groups receiving saline. Pain behavior was assessed using von Frey filaments at baseline and 1 h post-injection. For MEG recording, anesthetized rats had an OPM positioned on their head within a magnetic shield, undergoing two 15-minute sessions: a 5-minute baseline followed by a 10-minute mechanical stimulation phase. Data analysis included artifact removal and time-frequency analysis of spontaneous brain activity using accumulated spectrograms, generating spectrograms focused on the 4-30 Hz frequency range. ResultsMEG recordings in anesthetized rats during resting states and hind paw mechanical stimulation were compared, before and after saline/CFA injections. Mechanical stimulation elevated alpha activity in both male and female rats pre- and post-saline/CFA injections. Saline/CFA injections augmented average power in both sexes compared to pre-injection states. Remarkably, female rats exhibited higher average spectral power 1 h after CFA injection than after saline injection during resting states. Furthermore, despite comparable pain thresholds measured by classical pain behavioral tests post-CFA treatment, female rats displayed higher average power than males in the resting state after CFA injection. ConclusionThese results imply an enhanced perception of inflammatory pain in female rats compared to their male counterparts. Our study exhibits sex differences in alpha activities following CFA injection, highlighting heightened brain alpha activity in female rats during acute inflammatory pain in the resting state. Our study provides a method for OPM-based MEG recordings to be used to study brain activity in anaesthetized animals. In addition, the findings of this study contribute to a deeper understanding of pain-related neural activity and pain sex differences.
3.Exploration of potential active ingredients and mechanism of action of Xihuang pill-medicated serum against glioma based on HPLC-Q-TOF-MS/MS, network pharmacology and experimental verification
Jing PAN ; Qi-hai ZHANG ; Hao-wen FAN ; Xia WANG ; Wei-feng YAO ; Hong-bin XU
Acta Pharmaceutica Sinica 2024;59(3):693-703
Qualitative analysis of the ingredients absorbed into blood and their metabolites of Xihuang pill (XHP) were conducted using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS/MS) technology. Network pharmacology was used to explore the potential anticancer mechanisms of the ingredients against glioma, and their specific mechanisms were validated through molecular docking and experimental verification. SD rats were intragastrically administered with XHP, and rat serum samples were collected. Ingredients absorbed into blood and their metabolites were identified based on the retention time of chromatographic peaks, accurate molecular mass, characteristic fragment ions, and comparisons with reference substances and literature data. PharmMapper and SwissTarget Prediction databases were used to obtain the targets of the XHP-medicated serum, while GeneCards, OMIM, PharmGKB, TTD, and DrugBank databases were used to obtain glioma disease targets. The "component-target" network relationship diagram was constructed using Cytoscape 3.9.1 software. The protein-protein interaction (PPI) network diagram was constructed using the STRING database, and the targets were analyzed using GO and KEGG analyses. Molecular docking was used to verify the binding ability of core targets with their corresponding compounds in XHP-medicated serum. The potential mechanism of the anti-glioma effect of 11-keto-
4.Correlation analysis between serum vitamin D level and central precocious puberty in girls
Yongzheng LOU ; Yanan XU ; Pingping ZHANG ; Jiewen PAN ; Dongmei GAN ; Shuni SUN
China Modern Doctor 2024;62(3):16-20
Objective To investigate the correlation between serum vitamin D level and central precocious puberty(CPP)in girls.Methods A total of 103 girls(case group)with central precocious puberty from Ningbo Woman and Children's Hospital and 53 healthy girls(control group)from health check-ups in Ningbo Women and Children's Hospital were collected as subjects.The serum levels of 25-hydroxyvitamin D3[25(OH)D3]in the two groups were detected by chemiluminescence method.The weight and height of girls in the case group were measured.The serum levels of follicle-stimulating hormone(FSH)and its peak value,luteinizing hormone(LH)and its peak value,estradiol(E2),prolactin(PRL),human chorionic gonadotropin(HCG)and thyroid function were measured by radioimmunoassay.The peak value of LH/FSH was calculated.B ultrasound examination of uterine adnexa was completed to calculate uterine volume and bilateral ovarian volume.According to the results of serum 25-(OH)D3,girls in the case group were divided into normal vitamin D group and vitamin D deficiency group,and the differences of hormone levels,uterine and ovarian development between the two groups were compared.Results The serum level of 25-(OH)D3 in case group was lower than that in control group,and the vitamin D deficiency rate in case group was higher than that in control group,with statistical significance(P<0.05).The age of breast nodules in vitamin D deficiency group was lower than that in vitamin D normal group(P<0.05).There were no significant differences in body weight,height,body mass index(BMI),uterine volume and left ovarian volume between vitamin D normal group and vitamin D deficiency group(P>0.05),and the right ovarian volume in vitamin D deficiency group was significantly higher than that in vitamin D normal group(P<0.05).There were no significant differences in serum levels of FSH,LH,PRL,HCG,peak value of FSH and thyroid function between normal and deficient groups(P>0.05).The levels of E2,LH and LH/FSH in vitamin D deficiency group were significantly higher than those in vitamin D normal group(P<0.05);25-(OH)D3 was negatively correlated with LH/FSH peak(r=-0.197,P<0.05),but was not significantly correlated with thyroid function,FSH,LH,PRL,E2,HCG,FSH and LH peak(P>0.05).Conclusion Vitamin D deficiency is associated with central precocious puberty in girls.Vitamin D deficiency may lead to early onset of precocious puberty.Vitamin D deficiency may affect the hypothalamic-pituitary-gonadal axis function,resulting in changes in reproductive hormone indexes and consequent increase in ovarian volume in girls.
5.Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1α pathways.
Qiong ZHAO ; Luwen ZHANG ; Qiufen HE ; Hui CHANG ; Zhiqiang WANG ; Hongcui CAO ; Ying ZHOU ; Ruolang PAN ; Ye CHEN
Journal of Zhejiang University. Science. B 2023;24(1):50-63
Accumulating evidence has confirmed the links between transfer RNA (tRNA) modifications and tumor progression. The present study is the first to explore the role of tRNA methyltransferase 5 (TRMT5), which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma (HCC) progression. Here, based on bioinformatics and clinical analyses, we identified that TRMT5 expression was upregulated in HCC, which correlated with poor prognosis. Silencing TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro, which may be partially explained by declined extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Mechanistically, we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1 (HIF-1) signaling pathway by preventing HIF-1α stability through the enhancement of cellular oxygen content. Moreover, our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α. In conclusion, our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy drugs. Thus, TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.
Humans
;
Carcinoma, Hepatocellular/pathology*
;
Cell Hypoxia
;
Cell Line, Tumor
;
Gene Expression Regulation, Neoplastic
;
Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*
;
Liver Neoplasms/pathology*
;
Signal Transduction/genetics*
;
tRNA Methyltransferases/metabolism*
6.Protective effects of ginseng total saponins on reward-directed operant conditioning in hindlimb suspension rats
DONG Lijinchuan ; CHEN Ying ; HU Qin ; BAO Yu ; PAN Ruile ; ZENG Guirong ; PENG Bo ; LIU Xinmin ; SHI Zhe
Digital Chinese Medicine 2023;6(4):416-425
Objective:
To explore the therapeutic effects of ginseng total saponins (GTSs) on cognitive impairments in astronauts caused by prolonged exposure to microgravity environment.
Methods:
Fifty specific pathogen-free (SPF) male Wistar rats were randomized into control, hindlimb suspension (HLS), Huperzine A (HLS-Hup A 0.1 mg/kg), low-dose GTSs (HLS-GTSs 100 mg/kg), and high-dose GTSs (HLS-GTSs 200 mg/kg) groups, based on the completion time of reward-directed conditioning tasks. Except for rats in the control group, the others were subjected to HLS and treated with drugs (day 20 – 58), received reflex test under the condition of rewarding, and underwent Nissl body staining and Western blot detection on hippocampal.
Results:
After modeling, rats in HLS group exhibited a reduction in the number of lever presses and an increase in the completion time of the reward-directed operant conditioning task Ⅰ (P < 0.05) when compared with the control group, which were not substantially altered in the HLS-GTSs 100 and 200 mg/kg groups (P > 0.05). In the reward-directed operant conditioning task Ⅱ, the HLS group rats demonstrated a marked decrease in the number of lever presses (P < 0.05) and nose pokes (P < 0.01) when compared with the control group rats; the HLS-GTSs 100 mg/kg showed a significant increase in the number of lever presses and nose pokes (P < 0.05), while the HLS-GTSs 200 mg/kg demonstrated a significant reduction in completion time and an elevation in the number of lever presses (P < 0.05) when compared with the HLS group rats. In visual signal discrimination task, compared with the control group rats, the HLS group rats showed decrease in the indexes of the visual signal discrimination(P < 0.01), while HLS-GTSs 100 and 200 mg/kg groups exhibited manifest increase in it (P < 0.01). In reward extinction experiment, the number of lever presses in HLS rats significantly increased when compared with the control group (P < 0.01); compared with the HLS group,
HLS-GTSs 100 and 200 mg/kg groups demonstrated a marked descrease (P < 0.05). The expressions of N-methyl-D-aspartic acid receptor 1 (NR1) and phosophorylated N-methyl-Daspartic acid receptor 2B (p-NR2B) proteins were markedly decreased in rats in the HLS group (P < 0.05 and P < 0.01, respectively), while that of NR2B protein maintained the same (P > 0.05). GTSs increased the expression levels of p-NR2B (P < 0.01).
Conclusion
GTSs improved the learning and memory ability of complex operations by regulating the NR1/NR2B phosphorylation pathways in rats.
7.Research progress of caput femoris posterior tilt and its impact on prognosis in nondisplaced femoral neck fractures.
Rong-Yao YU ; Qing-Jiang PANG ; Xian-Jun CHEN ; Xiao YU ; Lin SHI ; Cheng-Hao WANG ; Sheng YU ; Chen-Tong PAN
China Journal of Orthopaedics and Traumatology 2023;36(10):969-974
There are still many unresolved problems in the treatment and prognosis of nondisplaced femoral neck fractures, such as nonunion and avascular necrosis of the caput femoris .In order to reduce the risk of various complications after non-displaced femoral neck fractures, the caput femoris posterior tilt of femoral neck fractures and its impact on prognosis have attracted more and more attention. A large number of scholars' studies have found that when the posterior tilt exceeds 20°, the risk of internal fixation failure increases significantly. Based on this concept, we can choose to use primary artificial joint replacement instead of three-screw internal fixation according to the different posterior tilt angles of patients to reduce the incidence of postoperative complications. At the same time, our analysis found that comminution of the posterior segment of the femoral neck would lead to an increase in the posterior inclination angles. The purpose of this review was to investigate the relationship between caput femoris posterior tilt of femoral neck fractures and surgical outcome, and to introduce a new method for measuring caput femoris posterior tilt of the femoral neck.
Humans
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Prognosis
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Postoperative Complications/epidemiology*
;
Femoral Neck Fractures/complications*
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Femur Neck
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Reoperation
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Fracture Fixation, Internal/methods*
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Retrospective Studies
8.Enlarged multicystic dysplastic kidneys with oligohydramnios during infancy caused by NPHP3 gene mutation.
Youwei BAO ; Xiaoli PAN ; Shuqing PAN ; Danyan ZHUANG ; Haibo LI ; Qitian MU ; Lulu YAN
Chinese Journal of Medical Genetics 2022;39(5):510-513
OBJECTIVE:
To explore the clinical features and genomic abnorm ality of a fetus enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation.
METHODS:
The fetuse was found to have multicystic dysplastic kidneys with oligohydramnios upon ultrasonography during the second trimester. Following induced abortion, fetal tissue was collected for the extraction of DNA, chromosomal microarray analysis (CMA) and whole exome sequencing (WES). Sanger sequencing was used to verify the suspected variants in the family.
RESULTS:
Antenatal ultrasound examination at 19 weeks showed "polycystic" kidneys with Oligohydramnios. Delivery was by induced labour because of the critically low amniotic fluid volume. Testing of CMA was normal. WES showed a compound heterozygous mutation of c.1817G>A, p.W606X; c.432dupA, p.E145Rfs*18 mutations are novel mutations in this study.
CONCLUSION
The research may further expand the NPHP3 gene mutation spectrum. Enlarged multicystic dysplastic kidneys with oligohydramnios caused by NPHP3 gene mutation at least include one or two splice site mutation, frameshift mutation or nonsense mutation foetal poor prognosis.
Amniotic Fluid
;
Female
;
Humans
;
Kidney Diseases, Cystic
;
Multicystic Dysplastic Kidney/genetics*
;
Mutation
;
Oligohydramnios/genetics*
;
Polycystic Kidney Diseases
;
Pregnancy
;
Ultrasonography, Prenatal
9.Association between daily average temperature and premature birth in Ningbo City: A time-series analysis
Mingming SHU ; Xuping ZHOU ; Shaohua GU ; Bailei ZHANG ; Xingqiang PAN
Journal of Environmental and Occupational Medicine 2022;39(6):679-683
Background Research on the relationship between ambient temperature and preterm birth has received increasing attention, but the conclusions of the previous literature are inconsistent. Objective To explore the impact of environmental temperature exposure in Ningbo on premature delivery of pregnant women. Methods The birth information, preterm birth data, and age of pregnant women from January 2016 to September 2020 were collected by the electronic medical record system of Ningbo Women’s and Children’s Hospital. Meteorological data for the same period were obtained through Ningbo Meteorological Bureau, including daily average temperature, daily average relative humidity, and daily average air pressure. Daily concentrations of SO2, NO2, and PM10 were derived through the air quality real-time release system on the website of Ningbo Environmental Protection Bureau. A distributed lag nonlinear model was used to analyze the impact of environmental temperature on preterm birth by stratifying pregnant women’s age and birth delivery mode. Results The incidence rate of preterm birth in Ningbo from 2016 to 2020 was 5.91%. The exposure-response curve between environmental temperature and preterm birth presented a “U” shape. Taking 22.5 ℃ as a reference, the cumulative effect of 31 ℃ (the 95th percentile) and 32 ℃ (the 99th percentile) over a 21-day lag on preterm delivery was statistically significant, and the related RR (95%CI) values were 1.67 (1.05-2.65) and 1.85 (1.09-3.14) respectively. The results of stratified analysis showed that among pregnant women ≥30 years old, the 21-day cumulative effects of 31 ℃ and 32 ℃ on preterm delivery were statistically significant, and the related RR (95%CI) values were 2.09 (1.08-4.05) and 2.36 (1.11-5.03) respectively; among pregnant women with natural delivery, the 21-day cumulative effect of 32 ℃ on preterm delivery was statistically significant, and the RR (95%CI) was 1.95 (1.02-3.74). Conclusion Exposure of pregnant women to high temperature during pregnancy could increase the risk of preterm birth, and there is a delayed cumulative effect.
10.Diagnosis a fetus with Coffin-Siris syndrome due to variant of SMARCA4 gene by whole exome sequencing.
Youwei BAO ; Xiaoli PAN ; Shuqing PAN ; Lisha GE ; Danyan ZHUANG ; Haibo LI
Chinese Journal of Medical Genetics 2022;39(12):1375-1378
OBJECTIVE:
To explore the clinical phenotype and genetic basis for a fetus suspected for Coffin-Siris syndrome.
METHODS:
Chromosomal microarray analysis (CMA) and whole exome sequencing (WES) were carried out for the fetus. Candidate variant was verified by Sanger sequencing.
RESULTS:
Prenatal ultrasound at 23rd gestational week has revealed fetal ventriculomegaly. No abnormality was found by CMA, while WES revealed that the fetus has harbored a de novo heterozygous c.2851G>A (p.G951R) variant of the SMARCA4 gene, which was predicted to be pathogenic.
CONCLUSION
Genetic testing should be considered for fetuses featuring progressive widening of lateral cerebral ventricles.
Female
;
Humans
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Pregnancy
;
DNA Helicases/genetics*
;
Fetus
;
Genetic Testing
;
Nuclear Proteins/genetics*
;
Phenotype
;
Transcription Factors/genetics*
;
Exome Sequencing

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