The effect of glutathione biosynthesis of Streptococcus thermophilus ST-1 on cocultured Lactobacillus delbrueckii ssp. bulgaricus ATCC11842.

Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus are the main species used for yogurt preparation. Glutathione (GSH) can be synthesized by S. thermophilus and plays a crucial role in combating environmental stress. However, the effect of GSH biosynthesis by S. thermophilus on cocultured L. delbrueckii ssp. bulgaricus is still unknown. In this study, a mutant S. thermophilus ΔgshF was constructed by deleting the GSH synthase. The wild strain S. thermophilus ST-1 and ΔgshF mutants were cocultured with L. delbrueckii ssp. bulgaricus ATCC11842 by using Transwell chambers (Guangzhou Shuopu Biotechnology Co., Ltd.), respectively. It was proven that the GSH synthesized by S. thermophilus ST-1 could be absorbed and used by L. delbrueckii ssp. bulgaricus ATCC11842, and promote growth ability and stress tolerance of L. delbrueckii ssp. bulgaricus ATCC11842. The biomass of L. delbrueckii ssp. bulgaricus ATCC11842 cocultured with S. thermophilus ST-1 or ΔgshF (adding exogenous GSH) increased by 1.8 and 1.4 times compared with the biomass of L. delbrueckii ssp. bulgaricus ATCC11842 cocultured with S. thermophilus ΔgshF. Meanwhile, after H2O2 and low-temperature treatments, the bacterial viability of L. delbrueckii ssp. bulgaricus cocultured with S. thermophilus ΔgshF, with or without GSH, was decreased by 41 and 15% compared with that of L. delbrueckii ssp. bulgaricus cocultured with S. thermophilus ST-1. Furthermore, transcriptome analysis showed that the expression levels of genes involved in purine nucleotide and pyrimidine nucleotide metabolism in L. delbrueckii ssp. bulgaricus ATCC11842 were at least 3 times increased when cocultured with S. thermophilus (fold change > 3.0). Moreover, compared with the mutant strain ΔgshF, the wild-type strain ST-1 could shorten the fermented curd time by 5.3 hours during yogurt preparation. These results indicated that the GSH synthesized by S. thermophilus during cocultivation effectively enhanced the activity of L. delbrueckii ssp. bulgaricus and significantly improved the quality of fermented milk.

[Construction and analysis of functional network of hemi-brain in patients with brain tumors before and after anesthesia based on resting-state functional magnetic resonance imaging].

Objective: To construct and analyze the functional network changes of hemi-brain in patients with brain tumor before and after anesthesia by using resting state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 18 right-handed patients were prospectively included (6 males and 12 females). The patients underwent glioma resection in Peking University International Hospital from December 2018 to December 2021, and age ranged from 20 to 65 (45.1±13.6) years, with American Society of Anesthesiologists (ASA) grade of Ⅰ-Ⅱ. MRI scans were performed while the patient was awake and at the depth of surgical anesthesia. The functional network of healthy lateral brain was constructed and analyzed by means of graph theory, and its global and local topological properties were calculated. Global topology attributes included global efficiency (Eg), local efficiency (Eloc), clustering parameters (Cp), length parameter of shortest path (Lp), and small world (SW). Topology attributes of nodes included node degree (ND), node efficiency (NE) and between centrality (BC). The global and nodal topological properties of the hemi-brain network were compared between patients with different hemispherical space occupying under wakefulness and anesthesia. Results: At the awake state, Eloc and Cp in the global topological attributes of hemi-brain network were 0.259±0.007 and 0.197±0.010, respectively, and decreased to 0.242±0.013 and 0.177±0.021, respectively after anesthesia, with statistically significant differences (all P<0.01). The topological attributes of the nodes in hemi-side brain showed that ND, NE and BC were increased in the default mode network-related brain regions, while NE and BC were decreased in the limbic system and subcortical structures. Eloc and Cp were 0.258±0.008 and 0.198±0.008 respectively in the patients with left hemisphere space occupying, and decreased to 0.241±0.011 and 0.177±0.015 respectively after anesthesia, with statistically significant differences (all P<0.01). However, only Eloc decreased in patients with right hemisphere space occupying after anesthesia, and Eloc was 0.260±0.006 and 0.243±0.016 respectively when awake and after anesthesia, with statistically significant differences (P<0.05). The topological attributes of nodes in patients with space occupying in different cerebral hemispheres showed bidirectional changes after anesthesia, and patients with space occupying in the left cerebral hemisphere were more likely to be widely affected after anesthesia. The effects of anesthetic drugs may show hemispheric laterality. If the tumor was in the dominant hemisphere, the compensatory function of the dominant side was more likely to be damaged. Conclusions: During anesthesia-induced loss of consciousness in patients with brain tumors, both the ability to integrate information and the functional connections between local regions are weakened, and some brain regions have functional connection reorganization. The changes of brain network after anesthesia are bidirectional regulation.

Microwave-field sensing via electromagnetically induced absorption of Rb irradiated by three-color infrared lasers.

A microwave electric field sensing has been set up based on a three-color electromagnetically induced absorption in rubidium vapor cell via cascading transitions. All transitions are irradiated by infrared lasers: a 780 nm laser servers as probe to monitor the optical transmittancy via transition 5S1/2→P3/2;, a 776 nm laser and a 1260 nm laser are used to couple the states 5P3/2 and 5D5/2 and states 5D5/2 and 44F7/2, respectively. We find that a frequency detuning ∼2π × ( - 40) MHz of the 776 nm dressing beam prefers to a better signal-to-noise ratio for the probe beam. The off-resonance greatly depresses the double resonance pumping effect. A demonstration measurement for the electric field of microwave 1.18988 GHz, corresponding to the coupling resonance between two adjacent Rydberg states 44F7/2 and 44F9/2, gives a sensitivity of 55.79(23)nVcm-1/Hz and a smallest discernible electric field of 78.9(33) nVcm-1 in time scale of 500 ms.

A food-grade vector for Streptococcus thermophilus based on the α-complementation of ß-galactosidase.

Streptococcus thermophilus is a common yogurt starter that consumes lactose as its primary carbon source. The enzyme ß-galactosidase is essential for the lactose metabolism and the growth of this species. Streptococcus thermophilus appears to be a promising cell factory. Food-grade vectors have advantages in heterologous protein expression. This study aimed to determine whether the ß-galactosidase of S. thermophilus has the α-complementary characteristic and to develop a novel food-grade vector based on this phenomenon. The N-terminal 7 to 36 AA residues of the ß-galactosidase in S. thermophilus were deleted. The obtained mutant S. thermophilus Δα lost ß-galactosidase activity and growth ability in the lactose medium. Subsequently, plasmids expressing α-fragments with different lengths of 1 to 36 (Sα1), 1 to 53 (Sα2), and 1 to 88 (Sα3) AA were constructed and transformed into S. thermophilus Δα. Recombinant S. thermophilus Δα expressing Sα2 or Sα3 recovered the ability to grow in the lactose medium, and their ß-galactosidase activity accounted for 24.5% or 11.5% of the wild strain, respectively. These results indicated that the α-complementation system of ß-galactosidase existed in S. thermophilus. Based on the characteristic, a food-grade vector pSEα was constructed. Except for Sα2, vector pSEα expressed the α-donor derived from E. coli ß-galactosidase. This facilitated the construction of recombinant plasmids in E. coli DH5α and thus improved the transformation efficiency of S. thermophilus. Green fluorescent protein as a reporter protein could be highly expressed in S. thermophilus using this vector. As a result, pSEα is an efficient and safe vector for S. thermophilus with potential food applications.

Peptide transporter-related protein 2 plays an important role in glutathione transport of Streptococcus thermophilus.

Streptococcus thermophilus is widely used as a starter culture in the fermentation of yogurt. Glutathione (GSH; γ-glutamyl-cysteinyl-glycine), as a tripeptide, has an important physiological role for Strep. thermophilus. However, the scope of the GSH transport proteins is still unexplored in this species. In the present study, 5 peptide transporter-related proteins (Ptrp) of Strep. thermophilus strain ST-1 were selected and then inactivated by gene insertion, respectively. Through detection and comparison of intracellular GSH content of mutant strain and wild strain, we identified 2 proteins, named Ptrp-2 and Ptrp-4, that might be related to GSH transport. Reverse-transcriptase quantitative PCR was performed to verify the gene expressions of these 2 possible GSH transport-related proteins, and it was finally determined that Ptrp-2 plays an important role in GSH transport of Strep. thermophilus. Milk fermentation experiments were further conducted to test the effect of Ptrp-2 on the characteristics of yogurt. The results showed that the fermented milk hardly curds using the mutant strain, indicating that Ptrp-2 is important for Strep. thermophilus as a yogurt starter.

Low-sugar yogurt making by the co-cultivation of Lactobacillus plantarum WCFS1 with yogurt starter cultures.

Yogurt making traditionally relies on the simultaneous utilization of 2 starters: Streptococcus thermophilus and Lactobacillus bulgaricus, but these 2 strains normally metabolize the glucose portion of lactose and release galactose into extracellular medium, resulting in high levels of residual galactose and unfermented lactose in yogurt, which leads to several industrial and health concerns. In this study, we found that Lactobacillus plantarum could effectively metabolize both lactose and galactose. Comparative genomic analysis demonstrated the constant presence of a chromosome-encoded Leloir pathway for galactose metabolism in Lb. plantarum species, and the gal operon was driven by a strong constitutive promoter in Lb. plantarum WCFS1, displaying great potential in low-sugar yogurt making. To test this hypothesis, Lb. plantarum WCFS1 was co-cultured with S. thermophilus or Lb. bulgaricus in lactose-based medium. Results showed that lactose was consumed completely and galactose was metabolized efficiently. For yogurt making, co-cultivation of Lb. plantarum WCFS1 with yogurt starter cultures produced a higher reduction of total sugar content compared with the traditional fermentation processes. In addition, the sensory analysis indicated that the yogurt fermented with yogurt starter cultures and Lb. plantarum WCFS1 was acceptable to consumers in appearance, texture, and flavor. Therefore, this study emphasized the potential to manufacture low-sugar yogurt by the co-cultivation of Lb. plantarum with yogurt starter cultures.

Artificial modulation-free Pound-Drever-Hall method for laser frequency stabilization.

We have proposed an artificial modulation-free Pound-Drever-Hall (PDH) method for laser frequency stabilization and demonstrated it via two-color polarization spectroscopy of Rydberg electromagnetically induced transparency (EIT) resonance in a room-temperature rubidium vapor. Due to the unique error signal profile, the conventional PDH method owns a large capture range in laser frequency locking. Here we manually construct a PDH error signal via a linear combination of polarization spectroscopies of the Rydberg EIT resonances without and with a magnetic field applied. The artificial modulation-free PDH error signal owns a subnatural linewidth dispersion curve as well as a large capture range with which we successfully stabilize the laser to an absolute atomic frequency reference in a long running time, immune to environmental fluctuation and even manmade impulse perturbation. This method can provide an absolute frequency reference based on atomic transition while keeping similar locking ability to provide corrections for frequency fluctuations over a broad bandwidth as the conventional PDH.

[Clinico-pathological features of temporal lobe epilepsy with enlarged amygdala].

OBJECTIVE: To summarize the clinical, video electroencephalogram (VEEG), radiological and pathological features of 3 patients of temporal lobe epilepsy (TLE) with amygdala enlargement (AE). METHODS: Three TLE patients with AE who were hospitalized in Peking University International Hospital were collected. The above features were retrospectively analyzed, and the amygdala volume was measured as well. RESULTS: Of all the 3 patients, 2 were females and 1 male, whose seizure onset ages varied from 21 to 40 years. Two cases presented with secondarily generalized tonicclonic seizures after falling asleep during the night. One of the 2 cases had complex partial seizures (CPSs) with episodic memory and automatism after one year, and the third one had CPSs with lip smacking and tongue wagging during the night. All the patients suffered from obvious anxious disorder. Unilateral AE by MRI was demonstrated in the 3 cases, one on the right side, and the other two on the left side. The average amygdala volume of the enlarged side and the other side were (2 123.7±131.8) mm3 and (1 276.3±156.9) mm3, respectively. Unilateral interictal epileptic discharges were ipsilateral to the AE in 2 cases, while the other patient showed bilateral interictal epileptic discharges. The ictal VEEG showed that the seizure onset zone was ipsilateral to the AE and was confined to the anterior and middle temporal regions in the 3 patients. The interictal single-photon emission computed tomography (SPECT) was negative in 2 cases. The interictal positron emission tomography (PET) showed hypometabolism in the AE in one case. The histological pathology revealed focal cortical dysplasia in the amygdala and temporal lobe in the 3 cases, and one of the 3 cases was combined with hippocampal sclerosis. All the patients became seizure free after surgery in the half year following-up. VEEG revealed slow wave activity and occasional spike wave in the operated side. CONCLUSION: AE may be one subtype of TLE. It is necessary to recognize AE in TLE with MRI-negative. For those poorly responsive to antiepileptic drugs, surgical treatment could provide a better solution. Focal cortical dysplasia may be one of the most common pathological features of TLE with AE.

Aspiration thrombectomy and intracoronary tirofiban in ST-segment elevation myocardial infarction : Combination treatment for patients undergoing primary percutaneous coronary intervention.

AIM: Primary percutaneous coronary intervention is the most effective treatment for patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to investigate whether the combination of aspiration thrombectomy with intracoronary tirofiban treatment can result in smaller infarcts and better patient prognosis compared with aspiration thrombectomy alone. PATIENTS AND METHODS: In all, 150 patients with STEMI underwent primary percutaneous coronary intervention. Group A received aspiration thrombectomy and group B received a combination treatment of aspiration thrombectomy with intracoronary tirofiban. The endpoint was major adverse cardiovascular events, including myocardial (re)infarction, cardiovascular death, and target vessel revascularization. RESULTS: The clinical characteristics of the groups were not significantly different (p > 0.05). The percentage of patients whose thrombolysis in myocardial infarction (TIMI) myocardial perfusion grades were less than 3 was significantly higher for group B than for group A (13.9 vs. 3.8 %, p = 0.029). The infarct size on cardiac magnetic resonance imaging was significantly different between groups (p = 0.036). At 6 months after the operation, the echocardiography results were better for patients in group B than for those in group A (p = 0.024 and p = 0.016, respectively). The frequency of bleeding complications and major adverse cardiac events of the groups were not significantly different (p > 0.05). CONCLUSION: Aspiration thrombectomy with intracoronary tirofiban in patients with STEMI is safe and effective. For cases with a large angiographic thrombus burden, tirofiban did not increase the rate of bleeding complications or major adverse cardiovascular events.

Genomic identification of group A bZIP transcription factors and their responses to abiotic stress in carrot.

The basic-region/leucine-zipper (bZIP) family is one of the major transcription factor (TF) families associated with responses to abiotic stresses. Many members of group A in this family have been extensively examined and are reported to perform significant functions in ABA signaling as well as in responses to abiotic stresses. In this study, 10 bZIP factors in carrot were classified into group A based on their DNA-binding domains. The cis-acting regulatory elements and folding states of these 10 factors were analyzed. Evolutionary analysis of the group A members suggested their importance during the course of evolution in plants. In addition, cis-acting elements and the folding state of proteins were important for DNA binding and could affect gene expression. Quantitative RT-PCR was conducted to investigate the stress response of 10 genes encoding the group A factors. Six genes showed responses to abiotic stresses, while four genes showed other special phenomenon. The current analysis on group A bZIP family TFs in carrot is the first to investigate the TFs of Apiaceae via genome analysis. These results provide new information for future studies on carrot.

The applicability of Ki-67 marker for renal epithelioid angiomyolipoma: experience of ten cases from a single center.

In order to present our experience with 10 cases of renal epithelioid angiomyolipoma (EAML) and validate the applicability of Ki-67 (proliferation marker) for EAML, we reviewed medical records of 10 consecutive cases diagnosed EAML from January 2005 to February 2012 at our department. Clinical data were collected and analyzed and pathology slides were reviewed. The immunohistochemical reactions for Ki-67 were performed and tumors showed positive expression were estimated. Active follow-up was performed to investigate the association between Ki-67 expression and the prognosis. The mean age and tumor size of the patients was 43.6 years (range 32-56) and 8.2 cm (range 2-15 cm), respectively. Seven were females while three were males. Radical nephrectomy was performed in 6 patients, partial nephrectomy in 3, and renal artery ligation in 1. The immunohistochemical reactions for HMB-45 (Human Melanoma Black), SMA (Smooth Muscle Actin) were positive but for S-100 were negative. The number of patients showing positive/negative Ki-67 expression was 5/5. The survival rate of the positive group was 20% (1/5) while 100% (5/5) of the negative group during the median follow-up time of 26.75 months (range 1-53). Recurrence, metastasis and death due to disease occurred in 1 (10%), 3 (30%) and 4 (40%) patients, respectively. Higher expression (positive) of Ki-67 indicates the presence of EAML and poor prognosis of patients. Surgical excision including radical and partial nephrectomy is a considerable approach to the treatment for its malignant potential.

Effect of Ezetimibe combined with Simvastatin in the treatment of coronary heart disease: a retrospective analysis.

OBJECTIVE: The aim of this study was to explore the effect of Ezetimibe combined with Simvastatin in the treatment of coronary heart disease (CHD). PATIENTS AND METHODS: Clinical data of 101 patients with CHD, admitted to our hospital from February 2022 to May 2023, were retrospectively analyzed. Among them, 49 patients received Simvastatin (Simvastatin group), and 52 patients received Simvastatin+Ezetimibe (Simvastatin+Ezetimibe group). Levels of blood lipid indicators, inflammatory factors, cardiac function indicators, and incidences of major adverse cardiovascular events (MACE) between the two groups were compared before and after the treatment. RESULTS: After the treatment, high-density lipoprotein cholesterol (HDL-C), cardiac index (CI), and left ventricular ejection fraction (LVEF) in both groups were higher than those before the treatment, and overall higher in the Simvastatin+Ezetimibe group. Levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), total cholesterol (TC), monocyte chemoattractant protein-1 (MCP-1), chemokine ligand 19 (CCL19), high sensitivity C-reactive protein (hs-CRP), cardiac output (CO) in the two groups were lower than before the treatment. These indexes were significantly lower in the Simvastatin+Ezetimibe group (p<0.05) compared to the Simvastatin group. During the treatment, the incidence of MACE in the Simvastatin+Ezetimibe group (3.85%) was significantly lower than that in the Simvastatin group (16.33%) (p<0.05). CONCLUSIONS: Compared with Simvastatin alone, a combination of Ezetimibe and Simvastatin can more effectively regulate the level of blood lipids, reduce the inflammatory reaction in the body, improve heart function, and lower the risk of MACE.

A two-degree-of-freedom hip exoskeleton device for an immature animal model of exercise-induced Legg-Calvé-Perthes disease.

Legg-Calvé-Perthes disease (LCPD) is a significant problem in healthcare because it so commonly affects young adults and immature athletes, primarily gymnasts. In this paper, a two-degree-of-freedom (2-DOF) hip exoskeleton device was developed for study on an immature animal model of exercise-induced LCPD. The exoskeleton device can reproduce the repetitive actions and forceful centrality impingements on the coxafemoral head that occur in sports such as gymnastics and acrobatics. It initiated a new method rather than the traditional medical or physiological operation method to establish an animal model of LCPD and allowed for the development and testing of new treatments. Ten immature New Zealand white rabbits were selected for the experiment. Their right legs were driven to achieve repetitive extension/ flexion and abduction/adduction beyond the normal range of motion, with centrality impingements at the maximum flexion position, while their left legs were kept in the initial healthy status and acted as the comparing reference. Four weeks later, the basic symptoms of early LCPD of the femoral head appeared. The results of X-ray, magnetic resonance imaging (MRI), gross anatomy observation, and H-E section also revealed it.

Genetic analyses of Chinese isolates of Toxoplasma gondii reveal a new genotype with high virulence to murine hosts.

A great deal of evidence demonstrates that a strongly clonal population structure of Toxoplasma gondii strains exists in humans and animals in North America and Europe, while the strains from South America are genetically separate and more diverse. Potential differences in virulence between different strains mean that an understanding of strain diversity is important to human and animal health. However, to date, only one predominant genotype, ToxoDB#9 (Chinese I), and a few other genotypes, including ToxoDB#205, have been identified in China. By using DNA sequence-based phylogenetic analyses, we have re-evaluated the population structure of T. gondii strains collected from China and compared them with other global strains. Based on phylogenetic analysis of restriction fragment length polymorphisms, multilocus sequence typing and intron sequences from T. gondii, we propose that the Chinese isolates described as Chinese I are divided into two groups called Chinese I and Chinese III. Our results demonstrate that significant differences were found in mouse mortality caused by some Chinese strains, and also the archetypal I, II, III strains in mice. Furthermore, a comparison of cyst loading in the brains of infected rats showed some Chinese strains to be capable of a high degree of cyst formation. Furthermore we show that genotyping using neutral genetic markers may not be a useful predictor of pathogenic phenotypes.

Establishment of a new animal model of azithromycin-induced liver injury and study the molecular pathological change during the process.

The purpose of the present study is to establish a new animal model of azithromycin (AZ)-induced liver injury and study the molecular pathological change during the process. First, mice were respectively injected intraperitoneally with AZ of different high doses. Our results showed that 800 mg/kg AZ injection significantly induced liver injury in the mice, which reflected an ideal process of liver injury and repair. In this study, we analyzed the molecular pathological changes during the process by hematoxylin and eosin staining, immunohistochemistry, Western blot, and quantitative real-time reverse transcription polymerase chain reaction in the liver of mice at 0, 12, 24, 48, and 72 h after 800 mg/kg injection. Our results showed that the expression of heat shock protein 70, proliferating cell nuclear antigen, vascular endothelial growth factor, caspase 3, and cytochrome P450 2E1 were significantly differently expressed during liver injury induced by 800 mg/kg AZ in mice. Our results will be conducive for further study of the pathogenesis and prevention of drug-induced liver injury.

Apoptosome inactivation rescues proneural and neural cells from neurodegeneration.

Deficiency of the apoptosome component Apaf1 leads to accumulation of supernumerary brain cells in mouse embryos. We observed that neural precursor cells (NPCs) in Apaf1(-/-) embryos escape programmed cell death, proliferate and retain their potential to differentiate. To evaluate the circumstances of Apaf1(-/-) NPC survival and investigate their fate under neurodegenerative conditions, we established cell lines of embryonic origin (ETNA). We found that Apaf1(-/-) NPCs resist common apoptotic stimuli and neurodegenerative inducers such as amyloid-beta peptide (typical of Alzheimer's disease) and mutant G93A superoxide dismutase 1 (typical of familial amyotrophic lateral sclerosis). Similar results were obtained in Apaf1(-/-) primary cells. When death is prevented by Apaf1 deficiency, cytochrome c is released from mitochondria and rapidly degraded by the proteasome, but mitochondria remain intact. Under these conditions, neither activation by cleavage of initiator caspases nor release of alternative apoptotic inducers from mitochondria takes place. In addition, NPCs can still differentiate, as revealed by neurite outgrowth and expression of differentiation markers. Our findings imply that the mitochondrion/apoptosome pathway is the main route of proneural and neural cells to death and that its inhibition prevents them from dismantling in neurodegenerative conditions. Indeed, the ETNA cell model is ideally suited for exploring the potential of novel cell therapies for the treatment of human neurodegenerations.

The important role of ADAM8 in the progression of hepatocellular carcinoma induced by diethylnitrosamine in mice.

This study focuses on investigating the concrete role of a disintegrin and metalloproteinase 8 (ADAM8) in the progression of hepatocellular carcinoma (HCC). Mice received anti-ADAM8 monoclonal antibody (mAb) of 100 µg/100 µl, 200 µg/100 µl or 300 µg/100 µl, respectively, in phosphate-buffered saline (PBS) or PBS intervention during the progression of HCC induced by diethylnitrosamine. The survival rate, body weight, and relative liver weight were determined in the mice. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and α-fetoprotein (AFP) level, hematoxylin-eosin staining, the expression level of vascular endothelial growth factor A (VEGF-A), proliferating cell nuclear antigen (PCNA), caspase 3 (Casp3), B cell leukemia 2 (Bcl2), B cell leukemia 2-associated X protein (Bax), protein p53 (P53), and ADAM8 were detected in the mice at the end of the 24th week. Our results showed that anti-ADAM8 mAb intervention effectively improved the survival rate, reduced the body weight loss and increased the relative liver weight in mice in a dose-dependent manner (p < 0.05 or p < 0.01). Anti-ADAM8 mAb intervention also significantly lowered serum AST, ALT, and AFP levels (p < 0.05 or p < 0.01), slowed the progression of HCC (p < 0.05 or p < 0.01), induced the expression of Casp3, Bax, and P53 (p < 0.05 or p < 0.01), and inhibited the expression of VEGF-A, PCNA, and Bcl2 in the liver of mice (p < 0.05 or p < 0.01) in a dose-dependent manner compared with the mice receiving PBS intervention. Our study suggested that ADAM8 might promote the progression of HCC by regulating the expression of these factors. Anti-ADAM8 mAb intervention might be suitable as a potential method for HCC therapy.

Lymphatic targeting of anti-HIV nucleosides: distribution of 2',3'-dideoxyinosine after intravenous and oral administration of dipalmitoylphosphatidyl prodrug in mice.

In the search for prodrugs of 2',3'-dideoxyinosine (ddI) with potential for improving the delivery of the nucleoside analogue to the lymphatic system, we synthesized dipalmitoylphosphatidyl-2',3'-dideoxyinosine (DPP-ddI) and its pharmacokinetics were investigated in mice. The disposition of ddI in plasma and lymph nodes was examined following intravenous and oral administration of parent nucleoside (100 mg/kg) and DPP-ddI (400 mg/kg, equivalent to 100 mg/kg of ddI). Concentrations of ddI were determined by HPLC. Pharmacokinetic parameters were estimated by area/moment analysis. Intravenous administration of DPP-ddI resulted in a pattern of lower peak concentrations of ddI and more sustained exposure of parent nucleoside in plasma and lymph nodes compared to administration of the parent nucleoside. Both ddI and DPP-ddI yielded similar AUC values in lymph nodes. Oral administration of the prodrug resulted in lower concentrations and AUC values of ddI in plasma and lymph nodes when compared to administration of the parent nucleoside. The bioavailability of ddI following ddI and DPP-ddI administration was 15 and 8%, respectively. The results of the present study demonstrate that DPP-ddI administered intravenously shows potential for targeting and sustaining level of ddI in the nodular lymphatic tissues.

Effect of diabetes and insulin treatment on nitric oxide synthase content in rat corpus cavernosum.

AIM: To study the effect of diabetes mellitus and insulin treatment on rat penile nitric oxide synthase content. METHODS: Male Wistar rats were divided at random into two groups: the Control (n = 8) and the Diabetic (n = 17). Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. The diabetic animals were then randomly divided into two subgroups: diabetic rats without insulin treatment (n = 7) and diabetic rats with insulin treatment (n = 10). The neuronal nitric oxide synthase (nNOS) in the penile corpus cavernosum were assayed by immumohistochemical staining with specific antibody to nNOS and the nNOS-positive nerve fibers were counted semiquantitatively under a high power microscope. RESULTS: The nNOS- positive nerve fibres in diabetic rats with treatment was higher than that in diabetic rats without treatment (P < 0.05) and lower than that in the controls (P < 0. 01). The nNOS-positive nerve fibres in diabetic rat without treatment were also lower than that in the controls (P < 0. 01). CONCLUSION: In streptozotocin-induced diabetic rats, the nNOS content in the penile corpus cavernosum was significantly decreased. Insulin treatment at the dose level employed partially restores the penile nNOS content in these rats.

Effects of unprocessed vs. cooked-processed Gastrodia elata on cytochrome P450 enzymes in rats.

CONTEXT: Gastrodia elata Blume (GE) has been used as a traditional herb and is considered one of the most important medicinal plants in Oriental countries since centuries. OBJECTIVE: The purpose of this study was to find out the differences between the effects of unprocessed and cooked-processed GE (CGE) on rat cytochrome P450 (CYP) enzymes (CYP1A2, CYP2C9 and CYP3A4) by using cocktail probe drugs in vivo. METHODS: A cocktail solution at a dose of 5 mL/kg, which contained phenacetin (20 mg/kg), tolbutamide (5 mg/kg) and midazolam (10 mg/kg), was orally administration to rats treated with GE or CGE for 14 days orally. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The corresponding pharmacokinetic parameters were calculated by the software of DAS 2.0. RESULTS: Both GE and CGE did not have significant influences on the pharmacokinetic parameters of phenacetin (P>0.05). In addition, CGE decreased the t1/2, Cmax, AUC(0-∞) of tolbutamide (P<0.05) and it increased CL significantly (P<0.01). Furthermore, the trend in CGE was similar but far more significant than GE on t1/2, Cmax, AUC(0-∞), and other parameters of midazolam (P<0.05). CONCLUSIONS: In conclusion, GE and CGE had no effects on rat CYP1A2. GE did not affect CYP2C9 activity, but CGE induced the CYP2C9 activity. Moreover, CGE was more potent than GE for inhibitory effect on CYP3A4 activity. These results provide useful scientific data for the safe clinical application of either extract of GE or in combination with other drugs, which should lack the side effects induced by other herb-drug interactions.