Activity of Semi-Synthetic Mulinanes against MDR, Pre-XDR, and XDR Strains of .

Tuberculosis causes more than 1.2 million deaths each year. Worldwide, it is the first cause of death by a single infectious agent.

Mulinane- and Azorellane-Type Diterpenoids: A Systematic Review of Their Biosynthesis, Chemistry, and Pharmacology.

Mulinane- and azorellane-type diterpenoids have unique tricyclic fused five-, six-, and seven-membered systems and a wide range of biological properties, including antimicrobial, antiprotozoal, spermicidal, gastroprotective, and anti-inflammatory, among others. These secondary metabolites are exclusive constituents of medicinal plants belonging to the , , and genera. In the last 30 years, more than 95 mulinanes and azorellanes have been reported, 49 of them being natural products, 4 synthetics, and the rest semisynthetic and biotransformed derivatives.

A Novel Intervention Platform for Service Members With Subjective Cognitive Complaints: Implementation, Patient Participation, and Satisfaction.

Introduction: Program overview of a novel cognitive training platform at Walter Reed National Military Medical Center (WRNMMC) for service members with subjective cognitive complaints: analysis of patient participation, satisfaction with the program, and perceived areas of improvement.

Materials And Method: Retrospective review of 1,030 participants from November 2008 through May 2017. Data were obtained within an approved protocol (WRNMMC-EDO-2017-0004/# 876230).

Disrupting MLV integrase:BET protein interaction biases integration into quiescent chromatin and delays but does not eliminate tumor activation in a MYC/Runx2 mouse model.

Murine leukemia virus (MLV) integrase (IN) lacking the C-terminal tail peptide (TP) loses its interaction with the host bromodomain and extraterminal (BET) proteins and displays decreased integration at promoter/enhancers and transcriptional start sites/CpG islands. MLV lacking the IN TP via an altered open reading frame was used to infect tumorigenesis mouse model (MYC/Runx2) animals to observe integration patterns and phenotypic effects, but viral passage resulted in the restoration of the IN TP through small deletions. Mice subsequently infected with an MLV IN lacking the TP coding sequence (TP-) showed an improved median survival by 15 days compared to wild type (WT) MLV infection.

Rotator Cuff Tear Susceptibility Is Associated With Variants in Genes Involved in Tendon Extracellular Matrix Homeostasis.

Rotator cuff tears (RCT) is a multifactorial disease with genetic factors contributing for the disease etiology. We hypothesized that genetic variants in genes involved in extracellular matrix (ECM) homeostasis may alter susceptibility to RCT. We evaluated 20 polymorphisms of genes involved in ECM homeostasis in 211 cases of full-thickness tears of the supraspinatus (N  = 130; N  = 81) and 567 age-matched controls (N  = 317; N  = 250).

The potential European genetic predisposition for non-contact anterior cruciate ligament injury.

Purpose: Previous research has provided evidence of a hereditary predisposition for anterior cruciate ligament (ACL) injury. The purpose of this study was to evaluate the association between ancestral population genetics and risk of non-contact ACL injuries.

Methods: Blood samples were collected from 177 individuals with a history of non-contact ACL injury and 556 non-injured control individuals for analysis of the genetic material through the use of a panel of 48 INDELs ancestry genetic markers from three ancestral origins.

Cardiovascular effects of SPARK conducted electrical weapon in healthy subjects.

Background: The increasing use of conducted electronic weapons (CEW) cause concern regarding its secure application, specially regarding the implications in the cardiovascular system.

Methods: The objective was to determine Spark CEW safety through cardiovascular parameters analysis of healthy volunteers subjected to its use.

Results: Volunteers over 18years without cardiovascular disease or recent use of illegal drugs were submitted, before and after being affected with Spark CEW, to clinical evaluation; blood collection for serum laboratory tests; transthoracic electrocardiography at rest, transthoracic echodopplercardiogram and 24hour Holter.

Primate dietary ecology in the context of food mechanical properties.

Substantial variation exists in the mechanical properties of foods consumed by primate species. This variation is known to influence food selection and ingestion among non-human primates, yet no large-scale comparative study has examined the relationships between food mechanical properties and feeding strategies. Here, we present comparative data on the Young's modulus and fracture toughness of natural foods in the diets of 31 primate species.

Detection and molecular characterization of double-stranded RNA viruses in Philippine Trichomonas vaginalis isolates.

Background/purpose: The flagellated protozoon Trichomonas vaginalis that parasitizes the urogenital tract of humans was reported to harbor double-stranded RNA (dsRNA) viruses. These viruses, identified as Trichomonas vaginalis virus (TVV), belong to the genus Trichomonasvirus of the family Totiviridae. Four species, formally recognized by the International Committee on Taxonomy of Viruses (ICTV), have been reported and distinguished by pairwise comparisons of the sequences of genes coding for major capsid protein (CP) and RNA-dependent RNA polymerase (RdRp).

Identification of Suitable Reference Genes for Investigating Gene Expression in Anterior Cruciate Ligament Injury by Using Reverse Transcription-Quantitative PCR.

The anterior cruciate ligament (ACL) is one of the most frequently injured structures during high-impact sporting activities. Gene expression analysis may be a useful tool for understanding ACL tears and healing failure. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) has emerged as an effective method for such studies.

Identification of suitable reference genes for gene expression studies in tendons from patients with rotator cuff tear.

Rotator cuff tear is one of the most common causes of shoulder dysfunction. Gene expression analysis may be a useful tool for understanding tendon tears and the failure of cuff healing, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies. However, this technique requires the use of suitable reference genes for data normalization.

Identification of suitable reference genes for gene expression studies of shoulder instability.

Shoulder instability is a common shoulder injury, and patients present with plastic deformation of the glenohumeral capsule. Gene expression analysis may be a useful tool for increasing the general understanding of capsule deformation, and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) has become an effective method for such studies. Although RT-qPCR is highly sensitive and specific, it requires the use of suitable reference genes for data normalization to guarantee meaningful and reproducible results.

Further mulinane and azorellane diterpenoids isolated from Mulinum crassifolium and Azorella compacta.

The new mulinane diterpenoids 1 and 2 were isolated from the EtOAc extract of Mulinum crassifolium, while the rearranged mulinane 5, which was isolated for the first time from a natural source, was isolated from Azorella compacta. Compounds 1-2 were prepared by semi-synthesis thorough acetylation of the diterpene 17-acetoxymulinic acid (3). A mechanism of reaction was proposed, while the structures of the new compounds were elucidated on the basis of comprehensive spectroscopic analysis and computational methods.

A new azorellane diterpenoid from Azorella madreporica.

A new azorellane diterpenoid has been isolated and identified from the aerial parts of Azorella madreporica Clos. The structure of 1 was established by one- and two-dimensional NMR techniques.

Diterpenoids from Azorella madreporica and their antibacterial activity.

Two new diterpenoids, mulin-12-en-16-al-20-oic acid and 13-α-hydroxy-mulin-11-en-14-one-20-oic acid, were isolated from Azorella madreporica. Their structures were identified on the basis of one-dimensional and two-dimensional NMR experiments. Their antibacterial activity was also tested.

(1R,3aR,5aS,6S,8aR,8bR,9aS)-1-Hydr-oxy-6-isopropyl-1,3a,5a-trimethyl-perhydro-cyclo-penta-[a]cyclo-propa[i]naphthalen-4-one.

The title compound (also know as azorellanone), C(20)H(32)O(2), is built up from three fused carbocycles, one five-membered ring and two six-membered rings. The five membered-ring has an envelope conformation, whereas the six-membered rings have a distorted half-chair and a twist-boat conformation. In the crystal, mol-ecules are linked by O-H⋯O inter-actions into zigzag chains with graph-set notation C(8) along [010].

An orthorhombic polymorph of mulinic acid.

THE TITLE COMPOUND [SYSTEMATIC NAME: (3S,3aS,10bR)-3-isopropyl-5a,8-dimethyl-2,3,4,5,5a,6,7,10,10a,10b-deca-hydro-endo-epidioxy-cyclo-hepta-[e]indene-3a(1H)-carboxylic acid], C(20)H(30)O(4), is a polymorphic form of a previously reported structure [Loyola et al. (1990 ▶). Tetra-hedron, 46, 5413-5420].

Antituberculosis activity of alkylated mulinane diterpenoids.

Natural azorellane and mulinane diterpenoids show antituberculosis activity, which is increased by methylation of their free carboxyl group. We have systematically investigated the effect of alkylation in this class of diterpenoids and found that the profile of bioactivity is relatively unaffected by the introduction of short alkyl groups, both linear and branched. In this investigation, three semisynthetic diterpenoids, 13 hydroxy-mulin-11-en-20-oic acid n-propyl ester (3) and the n-propyl (19) and n-butyl (20) esters of isomulinic acid, showed the strongest antituberculosis activity (MIC=6.

Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids.

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-alpha-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 microg/mL against both strains.

Antioxidant activity of 50% aqueous--ethanol extract from Acantholippia deserticola.

The antioxidant properties oí Acantholippia deserticola, a herb used in traditional northern Chilean medicine was studied using free radical-generating systems. The 50% aqueous-ethanol extract oí Acantholippia deserticola protected against non-enzymatic lipid peroxidation in microsomal membranes of rat, induced by an Fe++-ascorbate system and measured spectrophotometrically by the TBARS test, and had strong free radical scavenging capacities on stable ABTS and DPPH radicals. The results shows that the IC50 value of the 50% aqueous-ethanolic extract of A.

Microbial transformation of the diterpene mulin-11,13-dien-20-oic acid by Mucor plumbeus.

Two new mulinane-type derivatives: 16-hydroxy mulin-11,13-dien-20-oic (2) acid and 7alpha,16-dihydroxy mulin-11,13-dien-20-oic (3) acid were obtained by microbial transformation of mulin-11,13-dien-20-oic acid (1), along with tyrosol (4) using liquid cultures of Mucor plumbeus. The latter compound has not been previously identified in the genus Mucor. Structural elucidation of these metabolites was achieved using 1D- and 2D-NMR spectroscopy.

Antimicrobial activity of three baccharis species used in the traditional medicine of Northern Chile.

The antimicrobial activities of aqueous ethanol and chloroform extracts of three Baccharis species currently used in Northern Chile folk medicine for the treatment of several infectious and inflammatory disorders were tested against Gram-positive and negative bacteria and fungal spp. using the agar-disc diffusion assay. The results indicated that the activity was more pronounced against Gram-positive than against Gram-negative bacteria and yeast.

(3S,3aS,5aS,7S,8S,10aS,10bR)-7,8-Dihydr-oxy-3-isopropyl-5a,8-dimethyl-2,3,4,5,5a,6,7,8,10a,10b-deca-hydro-cyclo-hepta-[e]indene-3a(1H)-carboxylic acid.

The mol-ecule of the title compound, C(20)H(32)O(4), is built up from three fused five-membered, six-membered and seven-membered rings. The five-membered ring has an envelope conformation, whereas the six- and seven-membered rings have chair conformations. The crystal structure is stabilized by strong inter-molecular O-H⋯O hydrogen bonds, forming a three-dimensional network.

Methyl 5a-acetoxy-methyl-3-isopropyl-8-methyl-1,2,3,3a,4,5,5a,6,7,10,10a,10b-dodeca-hydro-7,10-endo-epidioxy-cylohepta-[e]indene-3a-carboxyl-ate.

The mol-ecule of the title compound, C(23)H(34)O(6), is built up from three fused carbocycles, one five-membered, one six-membered and one seven-membered. The five-membered ring has an envelope conformation, whereas the six-membered ring has a perfect chair conformation and the seven-membered ring has a boat conformation. Intra-molecular C-H⋯O hydrogen bonds together with van der Waals inter-actions stabilize the mol-ecular conformation.