Coping Self-Efficacy as a Potential Moderator of the Relationship Between Sexual Orientation and Negative Mental Health Outcomes

Sexual minority individuals (i.e., those who identify as a sexual orientation other than heterosexual) have consistently been linked to an increased risk of negative mental health outcomes. The process of coping can impact the content and severity of said outcomes, and one’s ability to cope is often predicted by the concept known as coping self-efficacy (i.e., one’s belief in his or her ability to cope). This study aimed to assess the effects of sexual orientation, coping self-efficacy, and their interactions on mental health by looking at different aspects of coping self-efficacy as potential moderating variables. Self-perceptions of coping skills were assessed across three domains; problem-solving, stopping of unpleasant thoughts and emotions, and garnering social support. Mental health variables were evaluated by using measures assessing depression, anxiety, suicidal thoughts/behaviors (STBs), and alcohol use. Archival data were collected via a large single time point survey. Data were gathered from a community sample consisting of members of the National Coalition for Sexual Freedom (NCSF), an organization dedicated to protecting the sexual freedom and privacy rights of consenting adults. Hypotheses were tested through t-tests, analyses of variance, and general linear modeling. Results evidenced an increased prevalence of mental health symptoms among sexual minority individuals when compared to heterosexual counterparts

Three-dimensional interactions analysis of the anticancer target c-src kinase with its inhibitors

Src family kinases (SFKs) constitute the biggest family of non-receptor tyrosine kinases considered as therapeutic targets for cancer therapy. An aberrant expression and/or activation of the proto-oncogene c-Src kinase, which is the oldest and most studied member of the family, has long been demonstrated to play a major role in the development, growth, progression and metastasis of numerous human cancers, including colon, breast, gastric, pancreatic, lung and brain carcinomas. For these reasons, the pharmacological inhibition of c-Src activity represents an effective anticancer strategy and a few compounds targeting c-Src, together with other kinases, have been approved as drugs for cancer therapy, while others are currently undergoing preclinical studies. Nevertheless, the development of potent and selective inhibitors of c-Src aimed at properly exploiting this biological target for the treatment of cancer still represents a growing field of study. In this review, the co-crystal structures of c-Src kinase in complex with inhibitors discovered in the past two decades have been described, highlighting the key ligand–protein interactions necessary to obtain high potency and the features to be exploited for addressing selectivity and drug resistance issues, thus providing useful information for the design of new and potent c-Src kinase inhibitors

Epidemiological overview of Hodgkin lymphoma across the Mediterranean Basin

The epidemiology of Hodgkin lymphoma (HL) has always been a source of fascination to researchers due to its heterogeneous characteristics of presentation. HL is an uncommon neoplasm of B-cell origin with an incidence that varies significantly by age, sex, ethnicity, geographic location and socioeconomic status. This complex pattern was also found to be replicated among Mediterranean basin populations. HL incidence rates progressively decreased from industrialized European countries such as France (ASR=2.61) and Italy (ASR=2.39) to less developed nations such as Albania (ASR=1.34) and Bosnia Herzegovina (ASR=1.1). Regarding HL mortality we have found that countries with the lowest incidence rates show the highest number of deaths from this cancer and viceversa. Finally, a wide gap in terms of survival was showed across the Mediterranean basin with survival rates ranged from 82.3% and 85.1% among Italian men and women, to 53.3 % and 59.3% among Libyan men and women, respectively. Factors such as the degree of socio-economic development, the exposure to risk factors westernization-related, the availability of diagnostic practices along with different genetic susceptibilities to HL may explain its variation across Mediterranean countries. Furthermore, the lack of health resources decisively contribute to the poor prognosis recorded in less developed region. In the future, the introduction of appropriate and accessible treatment facilities along with an adequate number of clinical specialists in the treatment of HL and other cancers are warranted in order to improve the outcomes of affected patients and treat a largely curable type of cancer in disadvantaged regions

Geranylgeraniol overcomes the block of cell proliferation by lovastatin in C6 glioma cells

It is well documented that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors prevent cultured mammalian cells from progressing through the cell cycle, suggesting a critical role for a mevalonate-derived product. Recently, it has been shown that free geranylgeraniol (GG-OH) and farnesol (F-OH) can be utilized by C6 glioma cells for protein isoprenylation. The ability of CC-OH and F-OH to restore protein geranylgeranylation or farnesylation selectively has enabled us to examine the possibility that mevalonate is essential for cell proliferation because it is a precursor of farnesyl pyrophosphate or geranylgeranyl pyrophosphate, the isoprenyl donors involved in the posttranslational modification of key regulatory proteins. In this study we report that CC-OH, as well as mevalonate, overcomes the arrest of cell proliferation of C6 glioma cells treated with lovastatin, as assessed by increased cell numbers and a stimulation in [H-3]thymidine incorporation. The increase in cell number and [H-3]thymidine incorporation were significantly lower when F-OH was added. Under these conditions [H-3]mevalonate and [H-3]GG-OH are actively incorporated into a set of isoprenylated proteins in the size range of small, GTP-binding proteins (19-27 kDa) and a polypeptide with the molecular size (46 kDa) of the smaller isoform of 2',3'-cyclic nucleotide 3'-phosphodiesterase. Analysis of the proteins metabolically labeled by [H-3]mevalonate and [H-3]GG-OH reveals the presence of labeled proteins containing geranylgeranylated cysteinyl residues. Consistent with geranylgeranylated proteins playing a critical role in the entry of C6 cells into the cell cycle, a (phosphonoacetamido) oxy derivative of GG-OH, a drug previously shown to interfere with protein geranylgeranylation, prevented the increase in cell number when mevalonate or GG-OH was added to lovastatin-treated cells. These results strongly suggest that geranylgeranylated proteins are essential for progression of C6 cells into the S phase of the cell cycle and provide the first evidence that the "salvage" pathway for the utilization of the free isoprenols is physiologically significant in the CNS

Allosteric modulators targeting cannabinoid cb1 and cb2 receptors: Implications for drug discovery

Allosteric modulators of cannabinoid receptors hold great therapeutic potential, as they do not possess intrinsic efficacy, but instead enhance or diminish the receptor's response of orthosteric ligands allowing for the tempering of cannabinoid receptor signaling without the desensitization, tolerance and dependence. Allosteric modulators of cannabinoid receptors have numerous advantages over the orthosteric ligands such as higher receptor type selectivity, probe dependence and biased signaling, so they have a great potential to separate the therapeutic benefits from side effects own of orthosteric ligands. This review aims to give an overview of the CB1 and CB2 receptor allosteric modulators highlighting the structure-activity relationship and pharmacological profile of each classes, and their future promise

Global trends in emotional distress

In this study, we examined emotional distress using annual representative survey data from 1.53 million individuals surveyed in 113 countries from 2009 to 2021. Participants reported whether they had experienced worry, sadness, stress, or anger during a lot of the previous day. Within-country estimates showed that the prevalence of feelings of emotional distress increased from 25 to 31% between 2009 and 2021, with those with low levels of education and income experiencing the largest increases in distress. On a global level, the pandemic period was characterized by an initial increase in distress in 2020 followed by recovery in 2021

Cyclosporin A blocks calcium-dependent pathways of gene activation

We have used an interleukin-2 (IL-2) promoter-CAT fusion gene to study activation of IL-2 gene expression by IL-1, phytohemagglutinin (PHA), phorbol myristate acetate (PMA), and calcium ionophore in the murine thymoma line EL4 and the human lymphoma line Jurkat. The two cell lines respond differently to combinations of these stimuli. IL-1 in combination with suboptimal concentration of PMA induced chloramphenicol acetyltransferase (CAT) activity in EL4. In Jurkat cells, IL-1 failed to synergize with PMA or PHA. Cotransfection with the IL-2/CAT gene and a construct capable of expressing murine T-cell type IL-1 receptors converted Jurkat cells to IL-1 responsiveness. IL-1 in combination with PHA but not with PMA resulted in induction of CAT activity in these cells. Induction of IL-2/CAT activity by all stimuli in both cell lines was blocked by the presence of EGTA in the culture medium. EGTA did not inhibit IL-1/PMA activation of an SV40 early promoter-CAT fusion gene in either EL4 or Jurkat cells; therefore, calcium was not required for IL-1 or PMA signal transduction. Jurkat cells were shown to differ from EL4 in their requirement for calcium mobilization. Two different calcium-dependent pathways of gene activation were distinguished, both of which were blocked by the immunosuppressive drug cyclosporin A

Medicinal Chemistry approach, pharmacology and neuroprotective benefits of CB2R modulators in neurodegenerative diseases

In the last decades, cannabinoid receptor 2 (CB2R) has continued to receive attention as a key therapeutic target in neuroprotection. Indeed, several findings highlight the neuroprotective effects of CB2R through suppression of both neuronal excitability and reactive microglia. Additionally, CB2R seems to be a more promising target than cannabinoid receptor 1 (CB1R) thanks to the lack of central side effects, its lower expression levels in the central nervous system (CNS), and its inducibility, since its expression enhances quickly in the brain following pathological conditions. This review aims to provide a thorough overview of the main natural and synthetic selective CB2R modulators, their chemical classification and their potential therapeutic usefulness in neuroprotection, a crucial aspect for the treatment of neurodegenerative diseases

A new catalytic and enantioselective desymmetrization of symmetrical methylidene cycloalkene oxides

Chiral copper complexes of C2-symmetrical hosphoroamidites were found to be highly effective catalysts for both kinetic resolution and novel desymmetrization reactions of new methylidene epoxycycloalkanes.