Phytochemical Constituents and Biological Activities of Plants from the Genus Cissampelos

Cissampelos is a significant genus comprising of approximately 21 species of the medicinal plants (Menispermaceae). The plants of this genus are used in traditional medicine for the treatment of various ailments such as asthma, arthritis, dysentery, hyperglycemia, cardiopathy, hypertension and other related problems. These plants are rich in bioactive dibenzylisoquinoline and aborphine as well as small amounts of other ingredients. In recent years, the chemical constituents and pharmacological activities of Cissampelos genus have been paid more and more attention due to their diversity. Herein, we compile the chemical constituents and biological activities on this genus, and summarize the ¹³C-NMR data of the main bioactive ingredients. All information comes from scientific databases such as Google Scholar, PubMed, Sci-Finder, ScienceDirect, Web of Science and CNKI. It provides valuable data for the future research and development of Cissampelos genus.     

Longitudinal virological changes and underlying pathogenesis in hospitalized COVID-19 patients in Guangzhou,China

Science China Life Sciences - Prolonged viral RNA shedding and recurrence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in coronavirus disease 2019 (COVID-19) patients have been...     

Sustainability of SARS-CoV-2 Induced Humoral Immune Responses in COVID-19 Patients from Hospitalization to Convalescence Over Six Months

Virologica Sinica - Understanding the persistence of antibody in convalescent COVID-19 patients may help to answer the current major concerns such as the risk of reinfection, the protection period...     

Photosynthetic temperature responses of four neem (Azadirachta indica A. Juss) provenances in the dry-hot valley area of China

The temperature dependences of net photosynthetic rate (P _N), stomatal conductance (g _s), transpiration rate (E) and dark respiration (R _D) of four neem (Azadirachta indica A. Juss) provenances of 11 years old were measured in three seasons of 2006 in the dry-hot valley area of southwest China under field conditions. The results indicated that P _N of four neem provenances showed clear parabolic responses with the increase of temperature. The optimum temperature of P _N was around 25°C in initiation stage and 30°C in prosperous stage except for neem originating from Jodhpur (MA) provenance which was very close to the mean daily temperature of the preceding week while it was around 27°C (MA provenance excepted) in last stage which was rather close to the mean daily maximum temperature of the preceding week. The optimum temperature for P _N of MA provenance was about 2–4°C higher than that of the other three neem provenances in prosperous stage and last stage. According to the fitted parameters of photosynthetic temperature response curves, the photosynthetic performance in prosperous stage was more sensitive to temperature changes than that in initiation stage and last stage while the photosynthetic performance of neem originating from MA provenance was less sensitive to temperatures than that of neem originating from Kalyani, New Delhi and Kulapachta provenances in each growing stage. Furthermore, the temperature ranges for P _N of MA provenance were much wider than those of the remaining provenances in each growing stage. These differences in photosynthetic temperature acclimation between neem provenances not only reflected temperature regime of native habitats of these provenances but suggested that MA provenance could be more tolerant to extreme temperatures compared with the remaining provenances. The temperature response curves of g _s and E were generally similar in form in the same growing stage for all neem provenances; however, shape of the response curves in initiation stage and last stage was similar to parabolic curve while that in prosperous stage was similar to linear relation. The temperature for maximum g _s and E in initiation stage was close to the optimum temperature of P _N, but the maximum g _s reached at much lower temperature than P _N and E in last stage. The response of R _D to temperature increased exponentially with temperature; however, there were obvious differences in different growing stages. R _D in initiation stage was markedly higher than that in prosperous stage and last stage at a given temperature for four neem provenances. These results suggested that four neem provenances can acclimate to their growing environment through changed photosynthetic ecophysiological responses in course of subjecting to seasonal variation of temperature.     

Co-transfer of LEA and bZip Genes from Tamarix Confers Additive Salt and Osmotic Stress Tolerance in Transgenic Tobacco

In this study, the additive effects of a late embryogenesis abundant (LEA) gene and a basic leucine zipper (bZIP) gene on salt and osmotic stress in Tamarix plants were analyzed. The constructs containing one or both of the LEA and bZIP genes were transformed into tobacco. Northern blot analysis showed the genes were overexpressed under the control of the CaMV 35S promoter in both dual and single gene-transgenic tobacco lines. The effects of salt and osmotic stress in transgenic tobacco plant were investigated. Following exposure to NaCl, mannitol, and PEG6000 stress, dual gene-transgenic lines showed higher seed generation and growth rates than single gene-transgenic lines and the wild-type. In response to NaCl stress, the dual gene-transgenic lines showed lower malondialdehyde and higher leaf chlorophyll content than single gene-transgenic lines and the wild-type. These results suggested that the co-expression of LEA and bZIP resulted in an additive enhancement of stress tolerance in dual gene-transgenic tobacco.     

GPR54 deficiency reduces the Treg population and aggravates experimental autoimmune encephalomyelitis in mice

GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system. However, flow cytometry revealed a significant reduction in the peripheral regulatory T cell population and a moderate decrease in CD4 single-positive thymocytes in prepubertal Gpr54~(-/-) mice. These phenotypes were confirmed in chimeric mice with GPR54 deficient bone marrow-derived cells. In addition, we found elevated T cell activation in peripheral and thymic T cells in Gpr54~(-/-) mice. When intact mice were immunized with myelin oligodendrocyte glycoprotein, a more severe experimental autoimmune encephalomyelitis(EAE) developed in the Gpr54~(-/-) mice. Interestingly, aggravated EAE disease was also manifested in castrated and bone marrow chimeric Gpr54~(-/-) mice compared to the respective wild-type control,suggesting a defect in self-tolerance resulting from GPR54 deletion through a mechanism that bypassed sex hormones. These findings demonstrate a novel role for GPR54 in regulating self-tolerant immunity in a sex hormone independent manner.     

Synthesis and evaluation of a ring-constrained Hsp90 C-terminal inhibitor that exhibits neuroprotective activity

KU-596 is a second-generation C-terminal heat shock protein 90 KDa (Hsp90) modulator based on the natural product, novobiocin. KU-596 has been shown to induce Hsp70 levels and manifest neuroprotective activity through induction of the heat shock response. A ring-constrained analog of KU-596 was designed and synthesized to probe its binding orientation and ability to induce Hsp70 levels. Compound 2 was found to exhibit comparable or increased activity compared to KU-596, which is under clinical investigation for the treatment of neuropathy.     

Prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (ADC) when evaluation of higher doses in animals is limited by tolerability: Case study with an anti-CD33 ADC

For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions.