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This study reports an overview of the economic, social and environmental performance of the main South American countries (SAC) as measured by the Sustainable Society Index. This is a well-known composite indicator, composed of 21 indicators, grouped in seven categories, covering environmental, social and economic wellbeing dimensions. Thirteen European countries recently incorporated into the European Union (NEUC) are considered as a reference. The study covers the period 2006-2016. The South American Region features significant natural resources and plays an important role in the global economy. However, there is concern about the long-term sustainability of social and economic development, given the high rate of economic growth based on the production of low added-value primary products. Sustainable development requires reasonable balance between economic, social and environmental performance, as well as a sustained and balanced increase in performance associated with those fundamental dimensions. Moreover, it is important to agree on minimum performance levels for all performance indicators, taking into account particular social, economic and environmental realities. SAC feature a clear imbalance in some categories affecting the economic, social and environmental wellbeing dimensions, showing either stagnation or significant decrease in recent years. It can be concluded that in the light of findings reported here, South American countries are far from being on the pathway towards sustainable development. [ABSTRACT FROM AUTHOR]

The identification of novel genes related to biotic and abiotic stress in Nicotiana tabacum L. can contribute to the genetic improvement of plants around the world. The aim of this research was to identify novel genes in tobacco varieties, as well as the molecular characterization of some expressed sequences tags (ESTs) in some Cuban tobacco varieties and species. The microarray technology was used with ESTs for the construction of a cDNA library. The most interesting finding in this study was that 265 ESTs had never been reported before in vegetable species and one gene, the Transcriptional Controlled Tumor Protein (TCTP), had never been reported before in N. tabacum, with the studies about this gene being focused on human and animals mostly. The microarray results were confirmed using quantitative RT- PCR. TCTP and pathogenesisrelated protein 1 (PR-1) ESTs were used to design primers for the molecular characterization of some species and Cuban tobacco varieties. In the case of TCTP, six species and four varieties were characterized, and eight varieties for PR1. TCTP was only expressed in two species (Nicotiana glutinosa L. and Nicotiana tomentosiformis Goodsp.) and PR1, after a digestion, exhibited different bands for susceptible and resistant varieties. The detection of these genes in some species and Cuban tobacco varieties is the first step to go further in the molecular characterization of Cuban germoplasm. [ABSTRACT FROM AUTHOR]

Rice (Oryza sativa L.) is one of the most important crops in the world. For this reason it is necessary to know how plants respond to it and the possible modulation of their concentrations. The aim of this research was to evaluate through cDNA microarray the expression of expressed sequence tags obtained from the stem tissue in a variety of rice "Hangfeng" treated with applications of the phytohormone gibberellin for 36 hours. Gibibberellin is a hormone that controls several important aspects in the development of plants. Thus, to go deepen in knowledge about this crop genome, an analysis of 2535 expressed sequence tags (ESTs) was done using microarray technology. Plants were previously treated with gibberelen phytohormone at 36 hours and stem tissue samples were taken when plants had from five to six leaves to proceed with total ARN extraction (Trizol method). A total of 1129 ESTs was classified into 18 functional categories according to the requirements established by the Munich Information Center for Protein Sequences (MIPS). Unique transcripts were involved in metabolism (18.5%) and energy (16. 19%) for a total of 214 and 181 ESTs respectively. As microarray result, 10 ESTs were generated at the 36 hour-treatment with the phytohormone, and four of those ESTs (Tubulin beta-1 chain, Auxin-responsive protein IAA16, Actin-depolymerizing factor 5 and Xyloglucan endotransglucosylase) had never been reported before in Oryza sativa L. Array results were confirmed using real time PCR. [ABSTRACT FROM AUTHOR]

Tobacco Mosaic Virus (TMV) is an economically important disease infecting crops worldwide. The objective of the present work was to evaluate the expression of representative sequences from N. tabacum genome in two Cuban tobacco varieties (BHmN and Corojo) with a different behavior in the pathogenic interaction. Leaf samples were taken at 0, 48 hours and seven days after virus inoculation to proceed with the total RNA extraction (Trizol method) and the primers were designed using sequences of tobacco defense genes to analyse their expression by RT-PCR. At seven days after inoculation, a β 1,3 glucanase expression was observed in both varieties, which was higher in the resistant one. Chitinase was induced at 48 h in the resistant variety with no expression seven days after inoculation. Phosphatase serine-threonine and the heat shock protein were expressed in both varieties at all the time tested; however the expression was a little higher in BHmN variety. In this study, the induction of β 1,3 glucanase in N. tabacum plants inoculated with TMV was likely to be related to the hypersensible response and the acquired systemic resistance. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death ligand 1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC) is a crucial factor in predicting responses to immunotherapy. This systematic review and meta-analysis focuses on the prevalence of PD-L1 expression and clinicopathological features among Hispanic/Latino (H/L) populations., Methods: Embase, LILACS, Medline, and Virtual Health Library were searched for studies that evaluated the prevalence of PD-L1 in H/L patients. The protocol was submitted to PROSPERO with ID CRD42023488547. We employed the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses to assess the methodological quality and applicability of the included studies. Meta-analyses were done to determine the prevalence using a random effects model., Results: The meta-analysis, encompassing 21 articles with 16,486, revealed that 80.2% of patients had PD-L1 expression data available (n=13,222). The prevalence calculated of PD-L1 expression in Latino NSCLC patients was 55% [95% confidence interval (CI): 0.54-0.55], with 31% (95% CI: 0.27-0.36) showing a tumoral proportion score (TPS) of 1-49%, and 23% (95% CI: 0.16-0.30) registering a TPS ≥50%. Higher expression was observed in male gender, smoking, adenocarcinoma subtypes, poor tumor differentiation, and advanced stages. PD-L1 expression was most frequent in EGFR wild-type status (82.5%) with a odds ratio (OR) 1.54 (95% CI: 1.24-1.92) and PD-L1 expression was associated with ALK positive (OR =1.54; 95% CI: 1.24-1.92)., Conclusions: This meta-analysis provides a comprehensive overview of PD-L1 expression in NSCLC in the H/L population. The findings underscore the significant prevalence of PD-L1 expression and emphasize the relevance of immunotherapy in this population. Understanding the clinicopathological features associated with PD-L1 expression can contribute to tailored treatment strategies for NSCLC in Latin America., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-223/coif). The authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Introduction: The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC., Methods: EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients. Meta-analyses were done to determine prevalence using a random effects model., Results: Fifty-five articles were included. EGFR and KRAS were the most prevalent genes with high heterogeneity across the countries. The overall mutation frequency for EGFR was 22%. The most frequent mutations in the EGFR gene were del19 (10%) and L858R (7%). The mean of KRAS mutation was a 14% prevalence. KRASG12C was the most frequent mutation with a 7% prevalence in an entire population. The overall frequency of ALK rearrangement was 5%. The mean frequency of ROS-1 rearrangement was 2%, and the frequencies of HER-2, MET, BRAF, RET, NTRK molecular alterations were 4%, 3%, 2%, 2%, and 1% respectively. Almost half of the cases were male, and 65.8% had a history of tobacco exposure. The most common clinical stage was IV., Conclusions: The prevalence of driver mutations such as EGFR and KRAS in LA populations differs from what is reported in Asians and Europeans. In the present article, countries with a high proportion of Amerindian ancestry show a greater prevalence of EGFR in contrast to countries with a high proportion of Caucasians. Lack of information on some countries or studies with a small sample size affects the real prevalence data for the region., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rafael Parra-Medina reports writing assistance was provided by University Foundation of Health Sciences. Rafael Parra-Medina reports a relationship with University Foundation of Health Sciences that includes: employment., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Brassinosteroids are plant hormones whose main function is to stimulate plant growth. However, they have been studied for their biological applications in humans. Brassinosteroid compounds have displayed an important role in the study of cancer pathology and show potential for developing novel anticancer drugs. In this review we describe the relationship of brassinosteroids with cancer with focus on the last decade, the mechanisms of cytotoxic activity described to date, and a structure-activity relationship based on the available information., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Glycogen synthase kinase 3 (GSK-3) is involved in different diseases, such as manic-depressive illness, Alzheimer's disease and cancer. Studies have shown that insulin inhibits GSK-3 to keep glycogen synthase active. Inhibiting GSK-3 may have an indirect pro-insulin effect by favouring glycogen synthesis. Therefore, the development of GSK-3 inhibitors can be a useful alternative for the treatment of type II diabetes. Aminopyrimidine derivatives already proved to be interesting GSK-3 inhibitors. In the current study, comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) have been performed on a series of 122 aminopyrimidine derivatives in order to generate a robust model for the rational design of new compounds with promising antidiabetic activity. The q 2 values obtained for the best CoMFA and CoMSIA models have been 0.563 and 0.598, respectively. In addition, the r 2 values have been 0.823 and 0.925 for CoMFA and CoMSIA, respectively. The models were statistically validated, and from the contour maps analysis, a proposal of 10 new compounds has been generated, with predicted pIC 50 higher than 9. The final contribution of our work is that: (a) we provide an extensive structure-activity relationship for GSK-3 inhibitory pyrimidines; and (b) these models may speed up the discovery of GSK-3 inhibitors based on the aminopyrimidine scaffold. Finally, we carried out docking and molecular dynamics studies of the two best candidates, which were shown to establish halogen-bond interactions with the enzyme.Communicated by Ramaswamy H. Sarma.

We report 31 new compounds designed, synthesized and evaluated on Bcr-Abl, BTK and FLT3-ITD as part of our program to develop 2,6,9-trisubstituted purine derivatives as inhibitors of oncogenic kinases. The design was inspired by the chemical structures of well-known kinase inhibitors and our previously developed purine derivatives. The synthesis of these purines was simple and used a microwave reactor for the final step. Kinase assays showed three inhibitors with high selectivity for each protein that were identified: 4f (IC 50 = 70 nM for Bcr-Abl), 5j (IC 50 = 0.41 μM for BTK) and 5b (IC 50 = 0.38 μM for FLT-ITD). The 3D-QSAR analysis and molecular docking studies suggested that two fragments are potent and selective inhibitors of these three kinases: a substitution at the 6-phenylamino ring and the length and volume of the alkyl group at N-9. The N-7 and the N -methyl-piperazine moiety linked to the aminophenyl ring at C-2 are also requirements for obtaining the activity. Furthermore, most of these purine derivatives were shown to have a significant inhibitory effect in vitro on the proliferation of leukaemia and lymphoma cells (HL60, MV4-11, CEM, K562 and Ramos) at low concentrations. Finally, we show that the selected purines ( 4i , 5b and 5j ) inhibit the downstream signalling of the respective kinases in cell models. Thus, this study provides new evidence regarding how certain chemical modifications of purine ring substituents provide novel inhibitors of target kinases as potential anti-leukaemia drugs.

A new series of twenty-two C-5 substituted N -arylsulfonylindoles was prepared with the aim of exploring the influence of C-5 substitution on 5-HT 6 receptor affinity. Eleven compounds showed moderate to high affinity at the receptor ( K i = 58-403 nM), with compound 4d being identified as the most potent ligand. However, regarding C-5 substitution, both methoxy and fluorine were detrimental for receptor affinity compared to our previously published unsubstituted compounds. In order to shed light on these observations, we performed docking and molecular dynamics simulations with the most potent compounds of each series ( 4d and 4l ) and PUC-10 , a highly active ligand previously reported by our group. The comparison brings about deeper insight about the influence of the C-5 substitution on the binding mode of the ligands, suggesting that these replacements are detrimental to the affinity due to precluding a ligand from reaching deeper inside the binding site. Additionally, CoMFA/CoMSIA studies were performed to systematize the information of the main structural and physicochemical characteristics of the ligands, which are responsible for their biological activity. The CoMFA and CoMSIA models presented high values of q 2 (0.653; 0.692) and r 2 (0.879; 0.970), respectively. Although the biological activity of the ligands can be explained in terms of the steric and electronic properties, it depends mainly on the electronic nature.

A series of 27 compounds of general structure 2,3-dihydro-benzo[1,4]oxazin-4-yl)-2-{4-[3-(1 H -3indolyl)-propyl]-1-piperazinyl}-ethanamides, Series I: 7 ( a - o ) and (2-{4-[3-(1 H -3-indolyl)-propyl]-1-piperazinyl}-acetylamine)- N -(2-morfolin-4-yl-ethyl)-fluorinated benzamides Series II: 13 ( a - l ) were synthesized and evaluated as novel multitarget ligands towards dopamine D 2 receptor, serotonin transporter (SERT), and monoamine oxidase-A (MAO-A) directed to the management of major depressive disorder (MDD). All the assayed compounds showed affinity for SERT in the nanomolar range, with five of them displaying K i values from 5 to 10 nM. Compounds 7k , K i = 5.63 ± 0.82 nM, and 13c , K i = 6.85 ± 0.19 nM, showed the highest potencies. The affinities for D 2 ranged from micro to nanomolar, while MAO-A inhibition was more discrete. Nevertheless, compounds 7m and 7n showed affinities for the D 2 receptor in the nanomolar range ( 7n : K i = 307 ± 6 nM and 7m : K i = 593 ± 62 nM). Compound 7n was the only derivative displaying comparable affinities for SERT and D 2 receptor (D 2 /SERT ratio = 3.6) and could be considered as a multitarget lead for further optimization. In addition, docking studies aimed to rationalize the molecular interactions and binding modes of the designed compounds in the most relevant protein targets were carried out. Furthermore, in order to obtain information on the structure-activity relationship of the synthesized series, a 3-D-QSAR CoMFA and CoMSIA study was conducted and validated internally and externally (q 2 = 0.625, 0.523 for CoMFA and CoMSIA and r 2 ncv = 0.967, 0.959 for CoMFA and CoMSIA, respectively).

1,4-Naphthoquinone derivatives have been widely documented with regard to their biological properties, and particularly their anticancer activities. In the 9,10-anthraquinone family, aza-annulation involving one of the carbonyl oxygen atoms has afforded more potent, possibly less toxic analogues. We recently carried out different modifications on the naphthoquinone skeleton to generate 3-chloro-2-amino- and 3-chloro-2-(N-acetamido)-1,4-naphthoquinone and 3,4-dihydrobenzo[f]quinoxalin-6(2H)-one derivatives. These three series of compounds were now tested against normal human fibroblasts and six human cancer cell lines. Some of the dihydrobenzoquinoxalinone derivatives were not only more potent than their 1,4-naphthoquinone counterparts, but also exhibited 10- to 14-fold selectivity between bladder carcinoma and normal cells and were equipotent with the non-selective reference drug used (etoposide). The fusion of an additional azaheterocycle to the 1,4-naphthoquinone nucleus modulates both the activity, selectivity and mechanism of action of the compounds. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with cytotoxic activity and mechanism of action. Finally, 3D-QSAR CoMFA and CoMSIA models were built on the AGS, J82, and HL-60 cell lines. The best models had values of r 2 pred  = 0.815; 0.823 and 0.925. The main structural relationships found, suggest that acetylation and alkylation of the amino group with large groups would be beneficial for cytotoxic activity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The spatial and temporal distribution of receptors constitutes an important mechanism for controlling the magnitude of cellular responses. Several members of the transient receptor potential (TRP) ion channel family can regulate their function by modulating their expression at the plasma membrane (PM) through rapid vesicular translocation and fusion. The mechanisms underlying this regulation are not completely understood, and the contribution of vesicular trafficking to physiological function is unknown. TRPM8 receptors are expressed in mammalian peripheral sensory neurons and are essential for the detection of cold temperatures. Previously, we showed that TRPM8-containing vesicles are segregated into three main pools, immobile at the PM, simple diffusive and corralled-hopping. Here, we show that channel expression at the PM is modulated by TRPM8 agonists in F11 and HEK293T cells. Our results support a model in which the activation of TRPM8 channels, located at the PM, induces a short-lived recruitment of a TRPM8-containing vesicular pool to the cell surface causing a transitory increase in the number of functional channels, affecting intrinsic properties of cold receptor responses. We further demonstrate the requirement of intact vesicular trafficking to support sustained cold responses in the skin of mice., (Copyright © 2015 the authors 0270-6474/15/350571-12$15.00/0.)

Sensory modalities are essential for navigating through an ever-changing environment. From insects to mammals, transient receptor potential (TRP) channels are known mediators for cellular sensing. Chlamydomonas reinhardtii is a motile single-celled freshwater green alga that is guided by photosensory, mechanosensory, and chemosensory cues. In this type of alga, sensory input is first detected by membrane receptors located in the cell body and then transduced to the beating cilia by membrane depolarization. Although TRP channels seem to be absent in plants, C. reinhardtii possesses genomic sequences encoding TRP proteins. Here, we describe the cloning and characterization of a C. reinhardtii version of a TRP channel sharing key features present in mammalian TRP channels associated with sensory transduction. In silico sequence-structure analysis unveiled the modular design of TRP channels, and electrophysiological experiments conducted on Human Embryonic Kidney-293T cells expressing the Cr-TRP1 clone showed that many of the core functional features of metazoan TRP channels are present in Cr-TRP1, suggesting that basic TRP channel gating characteristics evolved early in the history of eukaryotes., (© 2015 American Society of Plant Biologists. All rights reserved.)

The axon is a neuronal process involved in protein transport, synaptic plasticity, and neural regeneration. It has been suggested that their structure and function are profoundly impaired in neurodegenerative diseases. Previous evidence suggest that Peroxisome Proliferator-Activated Receptors-γ (PPARγ promote neuronal differentiation on various neuronal cell types. In addition, we demonstrated that activation of PPARγby thiazolidinediones (TZDs) drugs that selectively activate PPARγ prevent neurite loss and axonal damage induced by amyloid-β (Aβ). However, the potential role of TZDs in axonal elongation and neuronal polarity has not been explored. We report here that the activation of PPARγ by TZDs promoted axon elongation in primary hippocampal neurons. Treatments with different TZDs significantly increased axonal growth and branching area, but no significant effects were observed in neurite elongation compared to untreated neurons. Treatment with PPARγ antagonist (GW 9662) prevented TZDs-induced axonal growth. Recently, it has been suggested that the c-Jun N-terminal kinase (JNK) plays an important role regulating axonal growth and neuronal polarity. Interestingly, in our studies, treatment with TZDs induced activation of the JNK pathway, and the pharmacological blockage of this pathway prevented axon elongation induced by TZDs. Altogether, these results indicate that activation of JNK induced by PPARγactivators stimulates axonal growth and accelerates neuronal polarity. These novel findings may contribute to the understanding of the effects of PPARγ on neuronal differentiation and validate the use of PPARγ activators as therapeutic agents in neurodegenerative diseases.

Study Design: This study is a retrospective clinical investigation of a new interspinous device implanted via a totally percutaneous technique involving 152 consecutive patients., Objective: Evaluation of the efficacy of the percutaneous Aperius stand alone implant in patients with degenerative lumbar stenosis and neurogenic intermittent claudication that did not respond to conservative treatment., Summary of Background Data: The use of interspinous implants grew markedly during the last years. Nowadays, many extension controller devices are positioned through minimally invasive procedures., Methods: From January 2007 to February 2008, 152 consecutive patients with neurogenic intermittent claudication were treated with Aperius PercLID system. Under a local anesthesia, a 1.5 cm skin incision was performed. Trocars for interspinous space distraction were positioned using fluoroscopy guidance. A suitable size Aperius was positioned and released in the interspinous space with a totally percutaneous technique. In 145 patients 1 level was treated, whereas 6 patients received 2 level treatments, and 1 patient received 3 level treatments. The levels treated were L4-L5 in 125 patients (78.2%), L3-L4 level in 26 patients (16.3%), L2-L3 level in 5 patients (3.1%), L5-S1 level in 3 patients (1.8%), and L1-L2 level in 1 patient (0.6%)., Results: The surgical time ranged from 8 to 14 minutes for 1 single level. No adverse events were noted. In 1 case (0.6%), Aperius was not implanted because of hypertrophic facet joints that have hindered the correct insertion of the device; we observed only 2 cases of therapeutic failure (1.3%). There was a significant improvement in the Visual Analog Scale and Zurich Claudication Questionnaire scores for low-back and leg pain and for neurogenic claudication., Conclusions: These results indicate that Aperius PercLID system offers an easy, safe, and effective treatment for patients with lumbar degenerative stenosis. Thus, this device system treatment represents a valid alternative to the traditional surgical techniques.

Conventional open cervical discectomy, with or without bony fusion, in common neurosurgical knowledge is considered the standard treatment for cervical disc herniation. Percutaneous procedures are minimally invasive and offer decreased morbidity, require no bone graft and promise shorter recuperation time. Nevertheless, candidates for a percutaneous procedure as inclusion criteria must complain of symptoms related to contained herniated disc or focal protrusion. It does not substitute conventional open procedures required for extruded discs. We used the coblation technology for nucleoplasty of the cervical intervertebral discs. Early and long-term effects and/or complications observed with this procedure have not been reported yet. Fifty consecutive patients presenting with contained herniated cervical disc or focal protrusion causing compression of the cervical roots or cervical pain underwent a nucleoplasty procedure on the pathological disc. A randomized control group of twenty patients was treated conservatively with medical and physical therapy in the same period and completed the identical follow-up form. In the nucleoplasty group results were complete resolution of symptoms in 80% of cases, only 10% referred some residual cervical or radicular pain and are still under follow-up with a wait-and-see prospective. Patients who did not have a clinical resolution were treated with alternative traditional methods (10%). Despite the relative low cases number and the limited follow-up the encouraging results induce us to utilize this technique in well-selected cases.