Discovery and evolution of aloperine derivatives as novel anti-filovirus agents through targeting entry stage.

Preventing filoviruses in the entry stage is an attractive antiviral strategy. Taking aloperine, a Chinese natural herb with an endocyclic skeleton, as the lead, 23 new aloperine derivatives were synthesized and evaluated for their anti-filovirus activities including ebola virus (EBOV) and marburg virus (MARV) using pseudotyped virus model. Structure-activity relationship (SAR) analysis indicated that the introduction of a 12N-dichlorobenzyl group was beneficial for the potency. Compound 2e exhibited the most potent anti-EBOV and anti-MARV effects both in vitro and in vivo. It also displayed a good pharmacokinetic and safety profile in vivo, indicating an ideal druglike feature. The primary mechanism study showed that 2e could block a late stage of viral entry, mainly through inhibiting cysteine cathepsin B activity of host components. We consider compound 2e to be a promising broad-spectrum anti-filovirus agent with the advantages of a unique chemical scaffold and a specific biological mechanism.

Synthesis and Biological Evaluation of 12N-substituted Tricyclic Matrinic Derivatives as a Novel Family of Anti-Influenza Agents.

BACKGROUND: Influenza is still a serious threat to human health with significant morbidity and mortality, so it is desirable to develop novel anti-flu drug agents with novel structures. OBJECTIVE: The main purpose of this research was to explore broad-spectrum anti-flu agents and provide antiviral stockpiles in response to potential future influenza pandemics. METHODS: Fifteen novel 12N-substituted tricyclic matrinic derivatives were synthesized and evaluated for their anti-influenza activities against H1N1 subtype taking 12N-p-cyanobenzenesulfonyl matrinane (1) as the lead. All prepared compounds were characterized by 1H NMR, 13C NMR and ESI-HRMS. The pharmacokinetics (PK) profile of the key compound was also examined in this study. RESULT: The structure-activity relationship study indicated that suitable benzyl groups on 12N atom might be beneficial for the activity. Among them, 12N-p-carboxybenzyl matrinic butane (17g) exhibited the most promising activity with an IC50 value of 16.2 µM and a selective index (SI) value of over 33.4. In addition, compound 17g displayed a good in vivo pharmacokinetic profile with an area under the curve (AUC0-∞) value of 9.89 µM·h. CONCLUSION: We consider tricyclic matrinic butane derivatives to be a new class of anti-influenza agents and this study provided useful information on further optimization.

Up-regulation of TGF-ß1 mRNA expression in peripheral blood mononuclear cells of patients with chronic fatigue syndrome.

BACKGROUND/PURPOSE: It has been shown that the abnormality in immune cells in chronic fatigue syndrome (CFS) patients is closely associated with the participation of TGF-ß. In order to study the relationship between TGF-ß1 and CFS, we investigated the mRNA levels of TGF-ß1 in peripheral blood mononuclear cells (PBMCs) in patients with CFS. METHODS: Fluorescent quantitative real time reverse-transcription polymerase chain reaction (FQ-RT-PCR) was performed to test TGF-ß1 mRNA expression in PBMCs in 63 cases of CFS, 50 cases of disease controls, and 50 cases of healthy controls. RESULTS: The mean value of TGF-ß1 mRNA expression in CFS patients was ΔΔCt=1.17±0.58, which was significantly higher than the disease controls (ΔΔCt=0.07±1.08, df=111, p < 0.01) and the healthy controls (ΔΔCt=0.00±1.63, df=111, p < 0.01). No significant difference was detected between disease and healthy controls (p > 0.05). CONCLUSION: The expression of TGF-ß1 in PBMCs is significantly elevated in patients with CFS. It might be correlated to the pathogenesis of the disease.

[Crop root growth and water uptake in maize/soybean strip intercropping].

A field experiment was conducted to study the root distribution and water adsorption of maize and soybean in their strip intercropping. The results showed that under the condition of full irrigation, both maize roots and soybean roots were distributed approximately in triangle-shape in soil profile. Maize roots extended horizontally into a wider area, 58 cm away from the plant row and usually occurred in 16-22 cm soil layer. They were not restricted to maize root zone, but traversed into soybean strip zone. Soybean roots were horizontally distributed in a limited zone near the plant row, and their reached range was within about 26 cm. Both for maize and for soybean, their root mass density decreased with increasing distance from the plant row. About 90% of the root mass of maize and edge-row soybean was presented in 0-30 cm soil layer. The root mass density of maize at 10 cm from maize row was greater than that of soybean, but this density of soybean at 20 cm from maize strip was greater than that of maize. About 85% of root mass was distributed in 0-30 cm soil layer, and the variation of soil water content in intercropping strips also occurred mainly in this soil layer. In the maize/soybean strip intercropping system, soil water content decreased in the order of maize zone > soybean zone > middle zone, indicating that each strip-intercropped crop preferentially absorbed the soil water in its strip and utilized the soil water in intermingled zone later.

[Acute transverse myelitis associated with coxsackievirus B---A retrospective analysis of 7 patients].

OBJECTIVE: Acute Transverse myelitis (ATM) is a focal inflammatory disorder of the spinal cord, resulting in motor, sensory, and autonomic nerve dysfunction. There is often a clearly defined rostral border of sensory dysfunction. Nowadays, the pathogenesis of ATM is not clear. The present study aimed to understand possible relationship between ATM and infection with Coxsackievirus B. METHODS: IgM antibody against Coxsackievirus B was detected in cerebrospinal fluid of 33 patients with ATM. RESULTS: In 7 of the 33 cases with ATM, the IgM andtibody Coxsackievirus B (CVB) was positive. No infections with other pathogens were found at the onset of the disease. CONCLUSION: The pathogenesis of ATM may involve infection with Coxsackievirus B.

[Spatiotemporal distribution patterns of winter wheat and spring maize root systems under intercropping].

In this paper, root samples of winter wheat and spring maize under intercropping were taken with large-bore soil auger, and the dynamics of their spatiotemporal distribution were studied. The results showed that both in vertical and in horizontal directions, the root mass of winter wheat decreased in power function, while that of spring maize decreased in exponent function. Multiple linear regression was made to establish the two-dimensional spatiotemporal distribution functions of intercropped winter wheat and spring maize root biomass, and the validation tests demonstrated that theses functions were available to describe the real growth status of test crops root systems.

[Clinical characteristics of patients with chronic fatigue syndrome: analysis of 82 cases].

OBJECTIVE: To analyze the clinical characteristics of Chinese patients suffering from chronic fatigue syndrome (CFS) and provide clinical and laboratory evidence for the study of its etiology and treatment. METHODS: 82 patients with CFS diagnosed based on the CDC criteria 1994 were recruited. History was collected, and physical examination was made. SCL-90 and memory test were used, and Hamilton Anxiety Rating Scale was used to those showing depression and/or anxiety. Laboratory examination, including examination of electrolytes, blood sugar, creatinine, bilirubin, alkaline phosphatase, alanine trasaminase, etc, was conducted. Western blotting was used to detect the protein-24 of Borna disease virus (BDV) in the plasma of 61 patients and 73 healthy controls. High-pressure chromatography was conducted to detect n-6 fatty acids on the membrane of erythrocytes of 42 patients and 37 healthy controls. Plasma L-carnitine in 61 patients and 73 healthy controls was detected by zymological analysis. In different examinations sex and age-matched controls were used. RESULTS: Most of the patients were 21 approximately 50 years old (74/82, 90.24%). No gender difference was found. The patients usually had 4 approximately 6 symptoms besides distinctive fatigue. Descent of remembrance and/or attention was the most conspicuous accompanying symptoms (69/82, 84.15%). Abnormalities in SCL-90 scores were present in 57 patients (69.51%), e.g, somatization existed most commonly (32/82, 39.02%), and anxiety and depression were 20.73% (17/82) and 18.29% (15/82) respectively. The prevalence of anti-BDV-p24 antibody was 20.73% (17/82), significantly higher than that of the controls (0%, chi(2) = 6.673, P = 0.010). The arachidonic acid level was significantly lower in the CFS group than in the controls (P > 0.05) and there were no differences in linoleic acid and ETA (both P > 0.05). The level of L-carnitine was 6.4336 +/- 3.4225, significantly lower than that of the control group (7.6666 +/- 3.5819, t = 2.025, P = 0.045) and the L-carnitine level was increased 2 weeks after supplementary treatment, together with improvement of symptoms. CONCLUSION: Most of the CFS patients are young and middle-aged. Descent of reorganization is common in these patients. Psychological abnormalities exist in most patients. Some patients are infected with BDV, some with deficiency of nutrition and/or abnormality of energy metabolism.

[Detection of antibody against Borna disease virus-p24 in the plasma of Chinese patients with chronic fatigue syndrome by Western-blot analysis].

OBJECTIVE: To evaluate the prevalence of infection with Borna disease virus (BDV) in Chinese patients with chronic fatigue syndrome (CFS) and control subjects, and to discuss the etiological association between CFS and infection with BDV. METHODS: The CDC (1994) diagnostic criteria for CFS were used for case definition. Sixty-one patients suffered from CFS were from 11 Provinces in China. To detect the antibody against BDV-p24 on the plasma samples from all cases and 73 healthy control subjects by Western-blotting analysis. RESULTS: 7 of the sixty-one cases and 0 of the controls were sero-positive for BDV-p24 antibody, there was a statistical significant difference between the two groups (11.48% vs 0%; P less than 0.010). CONCLUSION: Chinese patients with CFS showed sero-positive identifying BDV infection, by comparison, anti.BDV-p24 antibody prevalence in patients was significantly higher than in controls. An etiological association may exist between CFS and BDV infection.