Four new diterpenoid alkaloids from Delphinium elatum

Diterpenoid alkaloids exhibit remarkable chemical properties and biological activities. Such compounds are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. Several diterpenoid alkaloid components from Delphinium elatum cv. Pacific Giant and their derivatives exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines. Phytochemical investigations on the seeds of D. elatum cv. Pacific Giant led to the isolation of four new C₁₉-diterpenoid alkaloids, melpheline (1), 19-oxoisodelpheline (2), N-deethyl-19-oxoisodelpheline (3), and N-deethyl-19-oxodelpheline (4). The isolated alkaloids were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS).     

16-epi-19-S-vindolinine,an indoline alkaloid from Catharanthus roseus

Studies on the alkaloids of Catharanthus roseus have resulted in the isolation of a new alkaloid, to which the structure of 16-epi-19-S-vindolinine has been assigned.     

Alkaloid production in Catharanthus roseus cell cultures: Isolation and characterization of alkaloids from one cell line

A detailed study of one cell line (coded as 943) of Catharanthus roseus cell cultures has revealed the presence of the following alkaloids: ajmalicine, vallesiachotamine, hörhammerinine, hörhammericine, vindolinine, 19-epi- vindolinine, 19-acetoxy-11-methoxytabersonine, 19-acetoxy-11 -hydroxytabersonine, 19-hydroxy- 11-methoxytabersonine, yohimbine and isositsirikine, together with dimethyltryptamine and a new strychnos-type alkaloid.     

Cucurbitacin 19-hydroxylase in Cucurbita maxima

The enzymatic hydroxylation of the C-19-methyl group of cucurbitacin B and D was observed in partly purified preparations obtained from the unripe fruit of Cucurbita maxima. Assay methods were developed and the pH optimum, cofactor requirements, and substrate specificity determined.     

New 19α-hydroxyursane-type triterpenes from the leaves of Meyna spinosa (= Vangueria spinosa), Rubiaceae

Two new 19α-hydroxyursane-type triterpenes, 2α,3α,19α,24,28-pentahydroxyurs-12-ene (1) and meyanthic acid, 3β-acetoxy-2β,19α,23-trihydroxyurs-12-en-28-oic acid (2) along with one new aliphatic ester, myricyl pentadecanoate (3) and five known compounds, 19α-hydroxyasiatic acid (4), oleanolic acid (5), myricyl alcohol (6), β-sitosterol (7) and its glycoside (8) were isolated from the methanolic leaf extract of Meyna spinosa Roxb. ex Link (= Vangueria spinosa Roxb., Rubiaceae). The structures of the new compounds were elucidated on the basis of extensive spectroscopic (including 2D NMR) analysis and comparison with literature. Except oleanolic acid, isolation of known compounds was reported for the first time from this plant.     

Gut Microbiome Alterations in COVID-19

Since the outset of the coronavirus disease 2019 (COVID-19) pandemic, the gut microbiome in COVID-19 has garnered substantial interest, given its significant roles in human health and pathophysiology. Accumulating evidence is unveiling that the gut microbiome is broadly altered in COVID-19, including the bacterial microbiome, mycobiome, and virome. Overall, the gut microbial ecological network is significantly weakened and becomes sparse in patients with COVID-19, together with a decrease in gut microbiome diversity. Beyond the existence of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the gut microbiome of patients with COVID-19 is also characterized by enrichment of opportunistic bacteria, fungi, and eukaryotic viruses, which are also associated with disease severity and presentation. Meanwhile, a multitude of symbiotic bacteria and bacteriophages are decreased in abundance in patients with COVID-19. Such gut microbiome features persist in a significant subset of patients with COVID-19 even after disease resolution, coinciding with ‘long COVID’ (also known as post-acute sequelae of COVID-19). The broadly-altered gut microbiome is largely a consequence of SARS-CoV-2 infection and its downstream detrimental effects on the systemic host immunity and the gut milieu. The impaired host immunity and distorted gut microbial ecology, particularly loss of low-abundance beneficial bacteria and blooms of opportunistic fungi including Candida, may hinder the reassembly of the gut microbiome post COVID-19. Future investigation is necessary to fully understand the role of the gut microbiome in host immunity against SARS-CoV-2 infection, as well as the long-term effect of COVID-19 on the gut microbiome in relation to the host health after the pandemic.     

Anhydrobartogenic acid and 19-epibartogenic acid,two triterpenes from Barringtonia speciosa

Two new triterpene dicarboxylic acids, isolated from the fruits of Barringtonia speciosa, have been identified as anhydrobartogenic acid and 19-epibartogenic acid by spectral and chemical evidence.     

Two new subspecies of Bacillus thuringiensis isolated in Japan: Bacillus thuringiensis subsp. kumamotoensis (serotype 18) and Bacillus thuringiensis subsp. tochigiensis (serotype 19)

Bacteriological and serological characteristics of three Bacillus thuringiensis isolates obtained in Japan were investigated. They formed typical rhomboidal parasporal inclusions but flagellar (H) antigens of these isolates were different from those of the known 17 H serotypes of B. thuringiensis. The three isolates were divided into two new serotypes (serotypes 18 and 19). The serotype 18 isolate (3–71) produced thermostable exotoxin and the inclusions of this isolate were toxic to larvae of the silkworm, Bombyx mori, but nontoxic to larvae of the mosquito, Aedes aegypti. The other isolate (119-72) belonging to serotype 18 produced inclusions nontoxic to larvae of B. mori and A. aegypti and did not produce thermostable exotoxin. However, other bacteriological properties of the isolate 119-72 were similar to those of the isolate 3–71. The serotype 19 isolate (117-72) produced inclusions nontoxic to larvae of B. mori and A. aegypti and did not produce thermostable exotoxin. Acid production from saccharose and the production of brownish purple pigment were observed in the two serotype 18 isolates, while neither of them was observed in the serotype 19 isolate. In other 29 biochemical properties tested, there was no difference among the three isolates. Based on these characteristics, the following two subspecies names are proposed: Bacillus thuringiensis subsp. kumamotoensis (serotype 18) for the type strain 3–71 and Bacillus thuringiensis subsp. tochigiensis (serotype 19) for the type strain 117-72.     

工布乌碱的结构

从工布乌头 (Aconitumkongboense)根中分出 17个去甲二萜生物碱 ,其中一种为大渡乌碱型C19 二萜生物碱新生物碱工布乌碱 (kongboendine) 1。由光谱法 (1H 和13 C NMR、2D NMR和MS)确定其结构。     

Phenolic diterpenoids of podocarpus ferrugineus and other podocarps

19-Hydroxyferruginol and 19-acetoxyferruginol, two new naturally occurring phenolic diterpenoids, have been isolated from the heartwood of Podocarpus ferrugineus. Totarol and its derivatives have been obtained from Podocarpus affinis, P. falcatus, P. koordersii, Dacrycarpus vieillardii and Decussocarpus comptonii and podocarpic acid from Falcatifolium taxoides.     

Fungal Infections in COVID-19 Intensive Care Patients

Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided.     

8β-hydroxypimar-15-en-19-oic acid from Taxodium mucronatum

A new diterpenoid has been isolated from the leaves and fruits of Taxodium mucronatum. Its structure, 8β-hydroxypimar-15-en- 19-oic acid, was established by chemical and spectroscopic means.     

Impact of Isolation measures on pregnancy outcome during the COVID-19 pandemic

This study aims to explore the impact of isolation measures implemented during the COVID-19 pandemic on childbirth outcomes in pregnant women. The design was a retrospective cohort study. The pregnant women during the outbreak lockdown and isolation from February 1 to April 30, 2020, were defined as the exposed population, and the pregnant women in the same time frame in 2019 as the non-exposed population. All data for the study were obtained from the National Health Care Data Platform of Shandong University. Generalized linear regression models were used to analyze the differences in pregnancy outcomes between the two study groups. A total of 34,698 pregnant women from Shandong Province, China in the data platform met the criteria and were included in the study. The proportions were 11.53% and 8.93% for macrosomia in the exposed and the non-exposed groups and were 3.47% and 4.37% for low birth weight infants, respectively, which were significantly different. They were 22.55% and 25.94% attributed to average exposed effect for macrosomia and low birth weight infants. Meanwhile, the mean weight and standard deviation of full-term infants in the exposure group were 3414.80 ± 507.43 g, which were significantly higher than in the non-exposed group (3347.22 ± 502.57 g, P < 0.001). The effect of exposure was significant in the third trimester. In conclusion, the isolation during the COVID-19 pandemic increases the birth weight of infants and the probability of macrosomia, regardless of which trimester in isolation a pregnant woman was, while the third trimester is the sensitive window of exposure. Our findings provide a basis for health care and policy development during pregnancy in COVID-19, due to COVID-19 still showing a pandemic trend around the world in 2022.     

Doping in sport: 3. Metabolic conversion of oral norethisterone to urinary 19-norandrosterone

The detection of 19 norandrosterone (19-NA) in a competitor's urine sample is taken as prima facie evidence of administration of nandrolone or other 19-norsteroid but a potential problem is that administration of norethisterone, a progestogen used for menstrual disorders and for hormonal contraception, also results in the excretion of 19-NA that can exceed the laboratory reporting threshold of 2 ng/mL. The contribution of norethisterone to urinary 19-NA with and without 19-norandrostenedione, a known norethisterone tablet impurity, requires evaluation. Preparations containing, either <2 ng or 1 μg 19-norandrostenedione impurity per 5 mg of norethisterone, administered to female volunteers (n = 10) in doses comparable to those used for menstrual disorders (5 mg three times daily for 10 days), resulted in maximal 19-NA concentrations of 51 and 63 ng/mL, respectively. The maximal concentration of 19-NA, 2 h post-administration of a single 1 μg dose of 19-norandrostenedione, was 2.4 ng/mL. These results prove unequivocally that norethisterone is metabolized to 19-NA and that there is only a minor contribution from the impurity 19-norandrostenedione. Administration to women (n = 30) of a single contraceptive tablet containing norethisterone (1 mg) with one of the highest proportions of the impurity 19-norandrostenedione (∼0.5 μg, 0.05%, w/w) resulted in a urinary 19-NA concentration of 9.1 ng/mL, with a maximum concentration ratio of 19-NA to the norethisterone metabolite 3α,5β-tetrahydronorethisterone of 0.36. We provide data that should remove the need for time-consuming follow-up investigations to consider whether doping with 19-norandrogens has occurred.     

The potential use of Drosophila as an in vivo model organism for COVID-19-related research: a review

The world urgently needs effective antiviral approaches against emerging viruses, as shown by the coronavirus disease 2019 (COVID-19) pandemic, which has become an exponentially growing health crisis. Scientists from diverse backgrounds have directed their efforts towards identifying key features of SARS-CoV-2 and clinical manifestations of COVID-19 infection. Reports of more transmissible variants of SARS-CoV-2 also raise concerns over the possibility of an explosive trajectory of the pandemic, so scientific attention should focus on developing new weapons to help win the fight against coronaviruses that may undergo further mutations in the future. Drosophila melanogaster offers a powerful and potential in vivo model that can significantly increase the efficiency of drug screening for viral and bacterial infections. Thanks to its genes with functional human homologs, Drosophila could play a significant role in such gene-editing studies geared towards designing vaccines and antiviral drugs for COVID-19. It can also help rectify current drawbacks of CRISPR-based therapeutics like off-target effects and delivery issues, representing another momentous step forward in healthcare. Here I present an overview of recent literature and the current state of knowledge, explaining how it can open up new avenues for Drosophila in our battle against infectious diseases.     

COVID-19 and Fungal infections: a double debacle

Fungal infections remain hardly treatable because of unstandardized diagnostic tests, limited antifungal armamentarium, and more specifically, potential toxic interactions between antifungals and immunosuppressants used during anti-inflammatory therapies, such as those set up in critically ill COVID-19 patients. Taking into account pre-existing difficulties in treating vulnerable COVID-19 patients, any co-occurrence of infectious diseases like fungal infections constitutes a double debacle for patients, healthcare experts, and the public economy. Since the first appearance of SARS-CoV-2, a significant rise in threatening fungal co-infections in COVID-19 patients has been testified in the scientific literature. Better management of fungal infections in COVID-19 patients is, therefore, a priority and requires highlighting common risk factors, relationships with immunosuppression, as well as challenges in fungal diagnosis and treatment. The present review attempts to highlight these aspects in the three most identified causative agents of fungal co-infections in COVID-19 patients: Aspergillus, Candida, and Mucorales species.     

Minisatellite polymorphisms of the SLC6A19: susceptibility in hypertension

The SLC6A19 is a human homolog of B⁰AT1 that encodes a neutral amino acid transporter. We examined the distribution of VNTR (variable number of tandem repeats; minisatellites) and conducted polymorphic analysis of SCL6A19 isolated from the genomic DNA of controls and multi-generational families. The SLC6A19 was found to contain seven blocks of minisatellites, 3 of which (SLC6A19-MS1, -MS4, and -MS7) showed polymorphism and were found to be transmitted through meiosis following Mendelian inheritance in seven families. These minisatellite polymorphisms may be useful markers for paternity mapping and DNA fingerprinting. Furthermore, we conducted a case-control study in which genomic DNA from 400 controls and 205 cases with essential hypertension was compared. A statistically significant association was identified between rare SLC6A19-MS7 alleles and the occurrence of hypertension (odds ratio, 7.87; 95% confidence interval, 0.88-70.66; and p = 0.028). These findings suggest that the rare SLC6A19-MS7 allele may be a risk factor for hypertension.     

Identification and characterization of a novel cell-penetrating peptide of 30Kc19 protein derived from Bombyx mori

Cell-penetrating peptides (CPPs) or protein transduction domains (PTDs) have attracted increasing attention due to their high potential to deliver various, otherwise impermeable, bioactive agents, such as drugs and proteins across cell membranes. A number of CPPs have been discovered since then. Recently, 30Kc19 protein has attracted attention because it was the first cell-penetrating protein that has been found in insect hemolymph. Here, we report a cell-penetrating peptide derived from 30Kc19 protein, VVNKLIRNNKMNC, which efficiently penetrates cells when supplemented to medium for mammalian cell culture. Moreover, like other CPPs, this “Pep-c19” also efficiently delivered cell-impermeable cargo proteins, such as green fluorescent protein (GFP) into cells. In addition to the in vitro system, Pep-c19 exhibited the cell-penetrating property in vivo. When Pep-c19 was intraperitoneally injected into mice, Pep-c19 successfully delivered cargo proteins into various organ tissues with higher efficiency than the 30Kc19 protein itself, and without toxicity. Our data demonstrates that Pep-c19 has a great potential as a cell-penetrating peptide that can be used as a therapeutic tool to efficiently deliver different cell-impermeable cargo molecules into the tissues of various organs.