Exercise Addiction and Major Depressive Disorder - Clinical Diagnoses and Longitudinal Course.

Background: People at risk of exercise addiction report increased symptoms of psychopathology. The aim of this study was to clinically assess the lifetime prevalence of depressive disorders in individuals at risk of exercise addiction and to determine whether depressive symptoms tend to precede or follow excessive exercising. Methods: Based on the Exercise Dependence Scale-21, a total of 31 individuals categorized at risk of exercise addiction underwent the Structured Clinical Interview for DSM-5 to assess major depressive disorder (MDD). Findings: The results showed 16 of the 31 participants suffered from MDD. The onset of MMD occurred in 10 participants after excessive exercising and in 5 before excessive exercising. In one participant, the symptom onset was unclear. Conclusion: MDD is far more prevalent in patients with exercise addiction compared to the general population and develops more often after the beginning of exercise addiction. Caution in the use of exercise to treat depression may be warranted.

Mental Disorders in Individuals With Exercise Addiction-A Cross-Sectional Study.

Background and Aims: Exercise addiction has not yet been designated as an addictive disorder in the DSM-5 due to a lack of detailed research. In particular, associations with other psychiatric diagnoses have received little attention. In this study, individuals with a possible exercise addiction are clinically assessed, in order to establish a profile of co-occurring psychiatric disorders in individuals with exercise addiction. Methods: One hundred and fifty-six individuals who reported exercising more than 10 h a week, and continued to do so despite illness or injury, were recruited for the study. Those who met the cut-off of the Exercise Dependence Scale (n = 32) were invited to participate in a screening with the Structured Clinical Interview for DSM-5 (SCID-5-CV) and personality disorders (SCID-5-PD). Additionally, an interview based on the DSM-5 criteria of non-substance-related addictive disorders was conducted to explore the severity of exercise addiction symptoms. Results: 75% of participants fulfilled the criteria for at least one psychiatric disorder. Depressive disorders (56.3%), personality disorders (46.9%) and obsessive-compulsive disorders (31.3%) were the most common disorders. Moreover, there was a significant positive correlation between the number of psychiatric disorders and the severity of exercise addiction (r = 0.549, p = 0.002). Discussion: The results showed a variety of mental disorders in individuals with exercise addiction and a correlation between the co-occurrence of mental disorders and the severity of exercise addiction. Exercise addiction differs from other addictive und substance use disorders, as obsessive-compulsive (Cluster C), rather than impulsive (Cluster B) personality traits were most commonly identified. Conclusions: Our results underscore the importance of clinical diagnostics, and indicate that treatment options for individuals with exercise addiction are required. However, the natural history and specific challenges of exercise addiction must be studied in more detail.

Mental disorders in individuals at risk for exercise addiction - A systematic review.

INTRODUCTION: Exercise addiction is one of several behavioral addictions which has not yet been designated as an addictive disorder in the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5). This is in part due to a lack of clarity concerning co-occurring mental disorders of individuals at risk for exercise addiction. The aim of this review is to summarise the spectrum of psychopathology in populations at risk of exercise addiction. METHODS: The MEDLINE, Web of Science and PsycINFO databases were searched. All studies from the date of database creation until February 2020 were considered eligible. Terms used were "exercise addiction" and other mental disorders mentioned in conjunction with substance-related and addictive disorders. Studies were included if they assessed risk for exercise addiction and at least one other mental disorder. RESULTS: Twenty studies were included. The disorders assessed were eating disorders (n = 14), depression (n = 6), anxiety (n = 4), other substance-related and addictive disorders (n = 5), and borderline personality disorder (n = 1). In thirteen of the studies, evidence was found for higher rates of at least one mental disorder (most commonly eating disorders, anxiety and other addictive disorders) in individuals at risk for exercise addiction, compared to those not at risk. CONCLUSIONS: Individuals at risk for exercise addiction show a broad range of mental disorders as assessed by self-report, which is in line with sufferers of other addictive disorders. Systematic psychological and clinical assessments in those at risk of exercise addiction are worthwhile, and will serve to characterize the mental health problems of individuals suffering from exercise addiction.

Hygrobafilomycin, a cytotoxic and antifungal macrolide bearing a unique monoalkylmaleic anhydride moiety, from Streptomyces varsoviensis.

A new bafilomycin-type macrolide, named hygrobafilomycin (6), was isolated by a bioassay-guided selection and fractionation from a terrestrial actinomycete, Streptomyces varsoviensis, along with three known derivatives, bafilomycin D (3), C1 (4) and C2 (5). The structure of hygrobafilomycin was fully established by MS and NMR analyses, revealing a hygrolidin-bafilomycin hybrid with an unusual monoalkylmaleic anhydride moiety. Hygrobafilomycin (6) shows strong antifungal, antiproliferative and cytotoxic activities. In a panel of 40 tumor cell lines, compound 6 shows high cytotoxic potency (mean IC(50)=5.3 n).

Aristolactams, 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil and other bioactive constituents of Toussaintia orientalis.

The new aristolactam alkaloid toussalactam {2-hydroxy-1,6-dimethoxy-5H-dibenzo[cdf]indol-4-one} and the known ones, namely aristolactam AII, aristolactam BII, piperolactam C and aristolactam FII; 1-(2-C-methyl-beta-D-ribofuranosyl)-uracil, 3,4,5-trimethoxyphenyl-beta-D-glucopyranoside, and three catechinoids were isolated from the cytotoxic Toussaintia orientalis Verdc stem and root bark extracts, and their structures established based on analysis of spectroscopic data. The aristolactams exhibited antimicrobial and antiinflammatory activity, aristolactam FII showing almost the same level of activity as the standard anti-inflammatory agent Indomethacin. The compounds also exhibited either mild or no antiproliferative and cytotoxic activities, except aristolactam FII that showed the same level of cytotoxicity as the standard drug Camptothecin. 1-(2-C-Methyl-beta-D-ribofuranosyl)-uracil, which is being reported for the first time as a natural product, was inactive in the antibacterial, antifungal, antiinflammatory, antiproliferative and cytotoxicity assays.

Botryorhodines A-D, antifungal and cytotoxic depsidones from Botryosphaeria rhodina, an endophyte of the medicinal plant Bidens pilosa.

An endophytic fungus (Botryosphaeria rhodina) was isolated from the stems of the medicinal plant Bidens pilosa (Asteraceae) that is known for its anti-inflammatory, antiseptic and antifungal effects. The ethyl acetate extract of the fungal isolate exhibits significant antifungal activity as well as potent cytotoxic and antiproliferative effects against several cancer cell lines. Activity-guided fractionation resulted in the isolation of a complex of four depsidones, botryorhodines A-D and the auxin indole carboxylic acid. Botryorhodine A and B show moderate to weak cytotoxic activities against HeLa cell lines with a CC(50) of 96.97 microM and 36.41 microM, respectively. In addition, they also show antifungal activity against a range of pathogenic fungi such as Aspergillus terreus (MIC 26.03 microM for botryorhodine A and 49.70 microM for B) and the plant pathogen Fusarium oxysporum (MIC 191.60 microM for botryorhodine A and 238.80 microM for B). A potential role of the endophyte in modulating fungal populations living within or attacking the host plant is discussed.

Cytotoxic, anti-proliferative and antimicrobial furanoditerpenoids from Stuhlmania moavi.

The furanoditerpenoids voucapane, voucapane-6alpha,7alpha-diol, voucapane-18,19-diol and 18-hydroxyvoucapan-19-al were isolated from the cytotoxic stem and root bark extracts of Stuhlmaniamoavi Verdc. (Ceasalpiniaceae) and their structures established based on analysis of spectroscopic data. The compounds exhibited anti-proliferative, cytotoxic, antibacterial and antifungal activities, 18-hydroxyvoucapan-19-al showing the highest anti-proliferative and cytotoxic properties. Voucapane-18,19-diol was only mildly active but the activity was enhanced for its 18,19-di-(4-methyl)-benzenesulphonate. Some of these results thus corroborate the traditional medicinal uses of the crude extracts for the treatment of skin infections.

Arousing sleeping genes: shifts in secondary metabolism of metal tolerant actinobacteria under conditions of heavy metal stress.

Numerous microbial habitats are strongly influenced by elevated levels of heavy metals. This type of habitat has developed either due to ore mining and metal processing or by pedogenesis above metal-rich base rocks. Most actinobacteria are soil-borne microbes with a remarkable capability for the synthesis of a broad variety of biologically active secondary metabolites. One major obstacle in identifying secondary metabolites, however, is the known phenomenon of sleeping gene clusters which are present, but silent under standard screening conditions. Here, we proceed to show that sleeping gene clusters can be awakened by the induction in heavy metal stress. Both, a chemical and a biological screening with extracts of supernatant and biomass of 10 strains derived from metal contaminated and non-contaminated environments was carried out to assay the influence of heavy metals on secondary metabolite patterns of metal tolerant actinobacteria. Metabolite patterns of cultures grown in complex and minimal media were compared to nickel (or cadmium) spiked parallels. Extracts of some strains grown in the presence of a metal salt displayed intense antibiosis against Escherichia coli, Mycobacterium smegmatis, Staphylococcus aureus and Candida albicans. Contrarily to the widely held opinion of metals as hindrance in secondary metabolism, metals thus can induce or enhance synthesis of possibly potent and medically relevant metabolites in metal tolerant strains. Hence, re-screening of existing strain libraries as well as identification of new strains from contaminated areas are valid strategies for the detection of new antibiotics in the future.

Plasticity in gilvocarcin-type C-glycoside pathways: discovery and antitumoral evaluation of polycarcin V from Streptomyces polyformus.

Gilvocarcin-type polyketide glycosides represent some of the most powerful antitumor therapeutics. Bioactivity-guided fractionation of a culture extract of Streptomyces polyformus sp. nov. (YIM 33176) yielded the known gilvocarcin V (2) and a novel related compound, polycarcin V (1). Structure elucidation by NMR and chemical derivatization revealed that the congener (1) features a C-glycosidically linked alpha-L-rhamnopyranosyl moiety in lieu of the D-fucofuranose. The concomitant production of two distinct furanosyl and pyranosyl C-glycosides that share the same aglycone is unprecedented in bacteria. A conversion of both isoforms via a quinone methide intermediate can be ruled out, thus pointing to two individual C-glycosylation pathways. Cytotoxicity profiling of polycarcin V in a panel of 37 tumor cell lines indicated significant antitumoral activity with a pronounced selectivity for non-small-cell lung cancer, breast cancer and melanoma cells. As the antiproliferative fingerprint is identical to that of actinomycin D, the known DNA interaction of gilvocarcins was established as a general principle of antitumorigenic activity.

Pyrrole and indole alkaloids from an endophytic Fusarium incarnatum (HKI00504) isolated from the mangrove plant Aegiceras corniculatum.

Two new pyrrole alkaloids, N-[4-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-butyl]-acetamide (1) and N-[5-(2-formyl-5-hydroxymethyl-pyrrol-1-yl)-pentyl]-acetamide (2), and a new indole derivative (3aR,8aR)-3a-acetoxyl-1,2,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol (3) were isolated, together with ( - )-3a-hydroxyfuroindoline, (3aR,8aS)-1-acetyl-1,3,3a,8,8a-hexahydropyrrolo-[2,3-b]indol-3a-ol, and N-acetyltryptamine A, from an endophytic ascomycetous fungus, Fusarium incarnatum (HKI00504), which was isolated from the mangrove plant Aegiceras corniculatum. The structures of compounds 1-3 were determined on the basis of extensive spectroscopic data analyses.

New abietane diterpenoids from the mangrove Avicennia marina.

Phytochemical investigations of the twigs of Avicennia marina yielded three new abietane diterpenoids 11-hydroxy-8,11,13-abietatriene 12- O-beta-xylopyranoside ( 1), and a pair of inseparable epimers 6 Halpha-11,12,16-trihydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial 11,6-hemiacetal ( 2) and 6 Hbeta-11,12,16-trihydroxy-6,7-secoabieta-8,11,13-triene-6,7-dial 11,6-hemiacetal ( 3), as well as the new lignan (7' S,8' R)-4,4',9'-trihydroxy-3,3',5,5'-tetramethoxy-7,8-dehydro-9-al-2,7'-cyclolignan ( 5), together with 6,11,12,16-tetrahydroxy-5,8,11,13-abitetetraen-7-one ( 4), lyoniresinol ( 6), lyoniresinol 9'- O-beta- D-glucopyranoside ( 7), and diacetylmartynoside ( 8). Structure elucidation of the new compounds was accomplished by analysis of their spectroscopic data. Compounds 2 - 4 showed moderate cytotoxic and antimicrobial activities.

Butyrolactone I derivatives from Aspergillus terreus carrying an unusual sulfate moiety.

In our ongoing search for new bioactive metabolites from microbial resources, Aspergillus terreus (HKI0499) was examined by chemical metabolite profiling. Together with the known butyrolactone I ( 3), the unusual sulfate derivatives butyrolactone I 3-sulfate ( 1) and butyrolactone I 4''-sulfate ( 2) were discovered. The chemical structures were determined by NMR and MS data analyses. All compounds were tested on CDK1/cyclin B, CDK5/p25, DYRK1A, CK1, and GSK-3alpha/beta kinases; compounds 2 and 3 were also evaluated for their cytotoxic and antiproliferative activities. Butyrolactone I 3-sulfate ( 1) exhibited specific inhibitory activity against CDK1/cyclin B and CDK5/p25, yet 15-30-fold less than butyrolactone I ( 3). Likewise, butyrolactone I 3-sulfate ( 1) exhibited moderate cytotoxicity solely against HeLa cells (CC 50 = 80.7 microM).

A-seco-oleane-type triterpenes from Phomopsis sp. (strain HKI0458) isolated from the mangrove plant Hibiscus tiliaceus.

From the fermentation broth of an unidentified Phomopsis sp. (strain HKI0458) isolated from the mangrove plant Hibiscus tiliaceus, four A-seco-oleane-type triterpenes, namely 3,4-seco-olean-11,13-dien-4,15alpha, 22beta,24-tetraol-3-oic acid (1), 3,4-seco-olean-11,13-dien-4,7beta,22beta,24-tetraol-3-oic acid (2), 3,4-seco- olean-13-en-4,7,15,22,24-pentaol-3-oic acid (3), and 3,4-seco-olean-13-en-4,15,22,24-tetraol-3-oic acid (4) were obtained. Their structures were elucidated by extensive spectroscopic (UV, IR, FABMS, and 2D NMR) data analyses.

Structure, derivatization, and antitumor activity of new griseusins from Nocardiopsis sp.

Four new griseusins, 4'-dehydro-deacetylgriseusin A (1) and 2a,8a-epoxy-epi-deacetylgriseusin B (2) as new constitutional derivatives and epi-deacetylgriseusin A (3) and epi-deacetylgriseusin B (4) as new stereoisomers, were isolated from Nocardiopsis sp. (YIM80133, DSM16644). 4'-Dehydro-deacetylgriseusin A (1) showed pronounced cytotoxic potency (mean IC50 = 0.430 microM) combined with a significant selectivity for mammary cancer, renal cancer, and melanoma in a panel consisting of 37 tumor cell lines. In a clonogenic assay with tumor cells from 51 solid tumors, 1 inhibited anchorage independent growth and in vitro colony formation of tumor cells in a concentration-dependent and tumor type selective manner. As 1 was only a minor product, a semisynthetic preparation from the major metabolite, epi-deacetylgriseusin A (3), was achieved. Our studies also yielded 9-hydroxy-epi-deacetylgriseusin B methylester (5), 4'-dehydro-9-hydroxy-deacetylgriseusin B methylester (6), and 4'-dehydro-2a,8a-epoxy-deacetylgriseusin B (7) as new synthetic isochromanequinone derivatives, which provided a basic structure-activity relationship study.

Cephalosporolides H and I, Two Novel Lactones from a Marine-Derived Fungus, Penicillium sp.

Two novel lactones, Cephalosporolides H (1) and 1 (2), were isolated from the lyophilized culture broth of the marine-derived fungus, Penicillium sp. The structures were elucidated on the basis of extensive 1D- and 2D-NMR, as well as HRESI-MS spectroscopic analyses. The relative stereochemistries of the compounds were assessed by comparison of the NOESY analysis and spectral data with those in the literature.

Abyssomicin E, a highly functionalized polycyclic metabolite from Streptomyces species.

Abyssomicin E (1), a new polycyclic metabolite with a C19 skeleton, was isolated from Streptomyces sp. (HKI0381). Its chemical structure was determined by comprehensive NMR and MS spectroscopic analyses. For the first time in this recently discovered class of compounds, the absolute stereochemistry was directly established by subsequent single-crystal X-ray diffraction study using anomalous dispersion with copper radiation.

Unusual naphthoquinone derivatives from the twigs of Avicennia marina.

In a continuing search for novel bioactive compounds from marine mangrove plants, seven new naphthoquinone derivatives were isolated from Avicennia marina, namely, avicennone A (1), avicennone B (2), avicennone C (3), avicennone D (4), avicenone E (5), avicennone F (6), and avicennone G (7), along with the known compounds avicequinone A (8), stenocarpoquinone B (9), avicequinone C (10), avicenol A (11), and avicenol C (12). The chemical structures of 1-7 were elucidated by spectroscopic methods. Compounds 8-10, and a mixture of 4 and 5, which all contain a 4,9-dione group, showed strong antiproliferative and moderate cytotoxic activities, as well as antibacterial effects.

Penisporolides A and B, two new spiral lactones from the marine-derived fungus Penicillium sp.

In our continued screening on bioactive constituents from marine-derived fungi, two novel compounds containing a rare spiral-lactone skeleton were isolated from lyophilized culture broth of the marine-derived fungus Penicillium sp. The structures of penisporolides A and B were elucidated on the basis of extensive 1D and 2D NMR as well as HRESI-MS spectroscopic data analysis. The relative stereochemistries of the compounds were assessed by analysis of NOESY data together with the comparison with data from previous literatures.

Griseusin C, a novel quinone derivative from a marine-derived fungus Penicillium sp.

A novel quinone derivative, Griseusin C (1), along with a known quinone, Naphthoquinone C (2), was isolated from the lyophilized culture broth of the marine-derived fungus Penicillium sp. The structures were elucidated on the basis of extensive 1 D- and 2D-NMR, as well as HRESI-MS, spectroscopic analysis. The relative stereochemistries of the compounds were assessed by NOESY analysis.