Exploring the Geroprotective Potential of Nutraceuticals.

Aging is the result of the accumulation of a wide variety of molecular and cellular damages over time, meaning that "the more damage we accumulate, the higher the possibility to develop age-related diseases". Therefore, to reduce the incidence of such diseases and improve human health, it becomes important to find ways to combat such damage. In this sense, geroprotectors have been suggested as molecules that could slow down or prevent age-related diseases. On the other hand, nutraceuticals are another set of compounds that align with the need to prevent diseases and promote health since they are biologically active molecules (occurring naturally in food) that, apart from having a nutritional role, have preventive properties, such as antioxidant, anti-inflammatory and antitumoral, just to mention a few. Therefore, in the present review using the specialized databases Scopus and PubMed we collected information from articles published from 2010 to 2023 in order to describe the role of nutraceuticals during the aging process and, given their role in targeting the hallmarks of aging, we suggest that they are potential geroprotectors that could be consumed as part of our regular diet or administered additionally as nutritional supplements.

Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Photoprotective effect of topical treatment with Lopezia racemosa extract against deleterious UVB irradiation effects in the skin of hairless mice.

Lopezia racemosa is known as a "mosquito flower or perlilla." It is commonly found in corn crops. In traditional Mexican medicine, this plant is used to treat stomach cancer and urinary tract infections. Likewise, compounds and extracts isolated from plants have shown cytotoxic and anti-inflammatory effects. The objective of this study was to evaluate the photochemoprotective effect of topical treatment with the methanolic extract of L. racemosa (MELR) as a photochemoprotective agent against the harmful effects of UV irradiation (UVR) on a bacterial model and hairless mice. The MELR components were separated and analyzed via HPLC-UV-ESI-MS. Antioxidant activity was evaluated by the ability of MERL to scavenge DPPH and ABTS free radicals and by its FRAP capacity. The toxicity of MELR was evaluated in keratinocyte cultures. The photoprotective capacity of MELR was assessed through challenge experiments using models with bacteria and hairless CD1 et/et mice; cytokines related to the damage caused by UVR were also measured. In the methanolic extract of L. racemosa, five metabolites were detected and identified: two isomers of quercetin 6-C glycoside, orientin, quercetin 3-(6″-acetylglycoside) and quercetin 3-(6″-galloylglycoside) 7-(2,3-dihydroxytetrahydro-2H-pyran-4-yl acetate). MELR exhibited DPPH and ABTS radical scavenging properties, in addition to Fe ion reducing activity. MELR showed a photoprotective effect against UVB radiation-induced death in Escherichia coli bacteria. At the histological level, topical treatment of CD-1 et/et mice with MERL reduced the damage caused by UVR. Quantification of interleukins in the blood of mice revealed that the expression of IL-12 was greater in the control group treated with ultraviolet radiation than in the group protected with MELR. The methanolic extract of L. racemosa has photochemoprotective properties.

Fatal acute undifferentiated febrile illness among clinically suspected leptospirosis cases in Colombia, 2016-2019.

BACKGROUND: Acute undifferentiated febrile illness is a common challenge for clinicians, especially in tropical and subtropical countries. Incorrect or delayed diagnosis of febrile patients may result in medical complications or preventable deaths. Common causes of acute undifferentiated febrile illness in Colombia include leptospirosis, rickettsioses, dengue fever, malaria, chikungunya, and Zika virus infection. In this study, we described the acute undifferentiated febrile illness in postmortem patients reported as suspected cases of leptospirosis through the national leptospirosis surveillance in Colombia, 2016-2019. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyze human fresh and formalin-fixed tissue samples from fatal suspected leptospirosis cases reported by the Public Health Laboratories in Colombia. Leptospirosis confirmation was made by immunohistochemistry, real-time polymerase chain reaction (PCR) in the tissue samples. In some cases, the serum sample was used for confirmation by Microagglutination test (MAT). Simultaneously, tissue samples were tested by PCR for the most common viral (dengue, Zika, and chikungunya), bacterial (Brucella spp., and Rickettsia spp.), and parasitic (malaria). Fresh tissue samples from 92 fatal suspected leptospirosis cases were reported to the National Reference Laboratory from 22/32 departments in Colombia. We confirmed leptospirosis in 27% (25/92) of cases. Other pathogens identified by real-time PCR were Brucella spp. (10.9%), Rickettsia spp. (14.1%), and dengue (2.2%). Dengue (6.9%), hepatitis (3.5%), and Yellow Fever cases (2.2%) were detected by the pathology. All patients were negative for chikungunya and Plasmodium spp. Most cases were classified as undifferentiated febrile illnesses (45.7%; 42/92). CONCLUSIONS/SIGNIFICANCE: This study underscores the importance of early and accurate recognition of leptospirosis to prevent mortalities. Moreover, it draws attention to the existence of other febrile syndromes in Colombia, including rickettsiosis and brucellosis, that currently lack sufficient human surveillance and regular reporting. Expanding laboratory surveillance to include viruses such as Hantavirus, Mayaro virus, Oropouche virus, and West Nile virus is crucial.

Unraveling the Neuroprotective Effect of Natural Bioactive Compounds Involved in the Modulation of Ischemic Stroke by Network Pharmacology.

Ischemic stroke (IS) is one of the leading causes of mortality worldwide. It is characterized by the partial or total occlusion of arteries that supply blood to the brain, leading to the death of brain cells. In recent years, natural bioactive compounds (NBCs) have shown properties that ameliorate the injury after IS and improve the patient's outcome, which has proven to be a potential therapeutic strategy due to their neuroprotective effects. Hence, in the present study, we use both systems pharmacology and chemoinformatic analyses to identify which NBCs have the most potential to be used against IS in clinics. Our results identify that flavonoids and terpenoids are the most studied NBCs, and, mainly, salidrosides, ginkgolides A, B, C, and K, cordycepin, curcumin, baicalin, resveratrol, fucose, and cannabidiol, target the main pathological processes occurring in IS. However, the medicinal chemistry properties of such compounds demonstrate that only six fulfill such criteria. However, only cordycepin and salidroside possess properties as leader molecules, suggesting that these compounds may be considered in developing novel drugs against IS.

Epigenetic Factors and ncRNAs in Testicular Cancer.

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

Multisystem Failure in Fatal Dengue: Associations between the Infectious Viral Serotype and Clinical and Histopathological Findings.

Dengue is the most important arthropod-borne viral infection of humans. However, its viral pathogenesis is still unknown. The information collected from dengue fatal cases is crucial for understanding the complex interactions between virulence and host factors. This study aimed to establish possible associations between the clinical characteristics, histopathological changes, replication, and tissue location of viral serotypes in dengue fatal cases. Clinical and histopathological characterizations, antigen localization in tissue, and detection of the infecting serotype and replication using real-time polymerase chain reaction were all performed on the dengue fatal cases. The majority of the cases involved people under the age of 20. Bleeding (48.3%), abdominal pain (44.8%), myalgia (52.9%), and headache (48.3%) were the most common clinical manifestations in the cases. There was multiorgan pathology, with histopathological changes primarily in the liver, spleen, and lung. Similarly, the viral antigen was found primarily in these organs; however, there were no associations between tissue changes, viral location, infecting serotypes, and replication processes. Dengue infection should be considered a multiorgan disease, the outcome of which is possibly not associated with the infecting viral serotype.

Genotyping of dengue virus from infected tissue samples embedded in paraffin.

Dengue has become one of the vector-borne diseases that affect humans worldwide. In Latin American countries, Colombia is historically one of the most affected by epidemics of this flavivirus. The underreporting of signs and symptoms of probable cases of dengue, the lack of characterization of the serotypes of the infection, and the few detailed studies of postmortem necropsies of patients are among other conditions that have delayed progress in the knowledge of the pathogenesis of the disease. This study presents the results of fragment sequencing assays on paraffin-embedded tissue samples from fatal DENV cases during the 2010 epidemic in Colombia. We found that the predominant serotype was DENV-2, with the Asian/American genotype of lineages 1 and 2. This work is one of the few reports of the circulating genotypes of dengue during the 2010 epidemic in Colombia, one of the most lethal dates in the country's history.

Fetal demise and SARS-CoV-2 infection during pregnancy: Histopathological and immunohistochemical findings of three cases referred to the Colombian National Institute of Health.

BACKGROUND: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection during pregnancy is related with adverse maternal, fetal, and neonatal outcomes. Placental SARS-CoV-2 involvement may include various degrees of inflammation and malperfusion leading to diverse pregnancy complications. METHODS: Placental, fetal and umbilical cord samples of three fetal demise cases that occurred in the context of maternal SARS-CoV-2 infections were analyzed. Cases were notified to the Colombian SARS-CoV-2 National Surveillance System. RT-PCR and immunohistochemistry (IHC) analysis were employed to identify potential tissue viral involvement. RESULTS: RT-PCR and IHC confirmed the presence of viral genomes and antigens in placental and umbilical cord tissues. Histopathological analysis revealed findings consistent with placental malperfusion and inflammation. CONCLUSIONS: SARS-CoV-2 infection during pregnancy can lead to placental dysfunction and damage compromising fetal survival. Many questions regarding SARS-CoV-2 dynamics during pregnancy including placental physiopathology and in utero transmission are still pending definitive answers.

Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

Antimicrobial activity of some macroalgae of the Veracruzano Reef System (SAV), Mexico.

The study of macroalgae antimicrobial agents is limited to Mexico and scarce in the Veracruzano Reef System (SAV). It is necessary to devote efforts towards this field of applied phycology. The aim was to evaluate the antimicrobial activity of some phyla of Rhodophyta, Chlorophyta and Ochrophyta from SAV. Methanolic extracts from 23 marine macroalgae species (7 Chlorophyta, 4 Phaeophyta and 12 Rhodophyta) from the Veracruzano Reef System (SAV) (Mexico) were evaluated for antimicrobial activity. Antibacterial and antifungal activity were assessed by agar diffusion and agar dilution methods. The differences between mean values obtained for experimental groups was done by analysis of variance (ANOVA multifactorial model), p-values of 0.001 or less were considered statistically significant. Two new records are recognized for SAV (Laurencia gracilis and Sebdenia flabellata) and Compsothamnion thuioides for the Gulf of Mexico coasts. 16 species showed antibacterial activity, of which Caulerpa sertularioides, Ulva lactuca and Laurencia obtuse had significant activity on Gram-positive bacteria. 43.7% belong to the phyla Chlorophyta (7 species), 50% Rhodophyta (8 species) and 6.25% Ochrophyta (1 species). This indicates that the extracts of the algae of the Rhodophyta and Chlorophyta are the ones that showed the greatest activity. Regarding the yeasts, 16.6% of the total algae collected were active in the different yeast strains. 43.7% belongs to Chlorophyta species and for Rhodophyta were 60%. The macroalgae with the highest antifungal activity were: Cymopolia barbata, Ulva lactuca and Laurencia gracilis. The macroalgae of the Veracruzano Reef System present antimicrobial activity. This study is the first investigation of macroalgae's bioactive components from SAV, where they could be sources for future medical applications.

Inmunohistochemical detection of pandemic SARSCoV- 2 antigens in lung tissue. / Detección inmunohistoquímica de antígenos de SARS-CoV-2 en tejido pulmonar

The COVID-19 pandemic caused by the SARS-CoV-2 virus has generated globally more than 110.7 million infections and 2.4 million deaths. The severity of this infection can range from asymptomatic, mild to severe. To know the possible associations between the presence of the virus and histopathological alterations found in tissues of fatal cases of COVID-19, the presence of the virus in the lung tissue of a patient with a clinical history of SARS-CoV-2 infection was evaluated. Lung tissue was histologically processed for immunohistochemical detection of SARSCoV-2. In the histopathological study, morphological changes associated with pneumonitis of viral origin were observed. Likewise, the location of the SARS-CoV-2 virus was observed mainly in the cytoplasm of the cells of the inflammatory infiltrate.

La pandemia de COVID-19 causada por el virus SARS-CoV-2 ha generado más de 110,7 millones de infecciones y 2,4 millones de muertes a nivel mundial. Esta infección puede ser asintomática y sus manifestaciones clínicas pueden variar entre leves y graves. Para conocer las posibles asociaciones entre la presencia del virus y las alteraciones histopatológicas encontradas en los tejidos de casos fatales de COVID-19, se evaluó la presencia del virus en el tejido pulmonar de un paciente con antecedentes clínicos de infección por SARS-CoV-2. La muestra se procesó para la detección inmunohistoquímica del virus. En el estudio histopatológico, se observaron cambios morfológicos asociados con neumonitis de origen viral. Asimismo, el virus se localizó principalmente en el citoplasma de las células del infiltrado inflamatorio.

Chemical profile, antimicrobial activity, and leaf anatomy of Adenophyllum porophyllum var. cancellatum.

Adenophyllum porophyllum var. cancellatum, known as "árnica del monte" in Mexico, is an aromatic annual plant belonging to the Asteraceae family that grows from southern Arizona to central Mexico. The aerial parts of the plant are used in traditional medicine to treat skin diseases such as irritations, infections, and wounds. In this study, the essential oil of this plant was characterized, and its antimicrobial activity was evaluated. This species has large glands in its leaves; therefore, for quality control purposes, an anatomical study of the leaves was performed. The essential oil was isolated from the aerial parts of the plant through hydro-distillation and analyzed using a gas chromatography/mass spectrometry (GC/MS) system. Its anti-yeast activity was evaluated against three Candida species and ten bacterial strains using the disk diffusion technique. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC) were determined using broth microdilution. Anatomical study was performed on the middle part of the leaf. A yield of 0.5% of the essential oil was obtained from the herb, and Eighteen compounds in the essential oil were identified, within them trans pinocamphone (29.5%), limonene (24.7%), pinocarvone (21.8%), and cis pinocamphone (8.0%) were the main components. The inhibition zones were between 10 mm and 20 mm, and the MIC and MFC against the three Candida species ranged from 60 to 500 µg/ml. The leaf anatomy showed anisocytic stomata, simple and glandular trichomes of different types, and large and elliptical-shaped lysigenous glands, which can be used for taxonomic identification. The A. porophyllum var. cancellatum essential oil can serve as an alternative source of natural antimicrobial agents as an affordable approach to control infectious diseases. This is the first study that reports the chemical composition and antimicrobial activity of the essential oil, as well as the leaf anatomy of this species.

Inmunohistochemical detection of pandemic SARS-CoV-2 antigens in lung tissue / Detección inmunohistoquímica de antígenos de SARS-CoV-2 en tejido pulmonar

The COVID-19 pandemic caused by the SARS-CoV-2 virus has generated globally more than 110.7 million infections and 2.4 million deaths. The severity of this infection can range from asymptomatic, mild to severe. To know the possible associations between the presence of the virus and histopathological alterations found in tissues of fatal cases of COVID-19, the presence of the virus in the lung tissue of a patient with a clinical history of SARS-CoV-2 infection was evaluated. Lung tissue was histologically processed for immunohistochemical detection of SARS- CoV-2. In the histopathological study, morphological changes associated with pneumonitis of viral origin were observed. Likewise, the location of the SARS-CoV-2 virus was observed mainly in the cytoplasm of the cells of the inflammatory infiltrate.

La pandemia de COVID-19 causada por el virus SARS-CoV-2 ha generado más de 110,7 millones de infecciones y 2,4 millones de muertes a nivel mundial. Esta infección puede ser asintomática y sus manifestaciones clínicas pueden variar entre leves y graves. Para conocer las posibles asociaciones entre la presencia del virus y las alteraciones histopatológicas encontradas en los tejidos de casos fatales de COVID-19, se evaluó la presencia del virus en el tejido pulmonar de un paciente con antecedentes clínicos de infección por SARS-CoV-2. La muestra se procesó para la detección inmunohistoquímica del virus. En el estudio histopatológico, se observaron cambios morfológicos asociados con neumonitis de origen viral. Asimismo, el virus se localizó principalmente en el citoplasma de las células del infiltrado inflamatorio.

Natural marine products as antiprotozoal agents against amitochondrial parasites.

The goal of this work is to compile and discuss molecules of marine origin reported in the scientific literature with anti-parasitic activity against Trichomonas, Giardia, and Entamoeba, parasites responsible for diseases that are major global health problems, and Microsporidial parasites as an emerging problem. The presented data correspond to metabolites with anti-parasitic activity in human beings that have been isolated by chromatographic techniques from marine sources and structurally elucidated by spectroscopic and spectrometric procedures. We also highlight some semi-synthetic derivatives that have been successful in enhancing the activity of original compounds. The biological oceanic reservoir offers the possibility to discover new biologically active molecules as lead compounds to develop new drug candidates. The molecular variety is extensive and must be correctly explored and managed. Also, it will be necessary to take some actions to preserve the source species from extinction or overharvest (e.g., by cryopreservation of coral spermatozoa, oocytes, embryos, and larvae) and coordinate appropriate exploitation to increase the chemical knowledge of the natural products generated in the oceans. Additional initiatives such as the total synthesis of complex natural products and their derivatives can help to prevent overharvest of the marine ecosystems and at the same time contribute to the discovery of new molecules.

Verbascoside-enriched fraction from Buddleja cordata Kunth ameliorates the effects of diabetic embryopathy in an animal model.

BACKGROUND: The deleterious effects of diabetes mellitus (DM) over development are apparently due to an increase in oxidative stress. Some antioxidants could prevent developmental alterations produced by diabetic state. Extracts of plants of the genus Buddleja are used traditionally for Mexican indigens to ameliorate some diseases. The purpose of this work was to evaluate the effect of the extract of Buddleja cordata over diabetic embryopathy. METHODS: Two experimental approaches were used: an in vivo study and an in vitro model. In the first, rats were treated with streptozotocin, streptozotocin plus methanolic extract of B. cordata, or none. Females were sacrificed at gestational day (GD) 19, and biochemical clinical parameters were measured; also, the fetuses were obtained and morphologically analyzed. In the in vitro model, a verbascoside-enriched fraction (VEF) of the extract was used in whole embryo culture in order to search for the mechanisms for embryoprotection effect over hyperglycemia-induced malformations. RESULTS: In the in vivo experiments, B. cordata extract reduces the frequency and severity of fetal malformations produced by chemically induced diabetes, and additionally partially ameliorates the diabetic condition; in the in vitro model, both severity and frequency of embryo dysmorphogenesis were reduced by the VEF; also, this fraction reduces lipoperoxidation without affecting the activity of the antioxidant enzymes. CONCLUSION: The results suggest that verbascoside of methanolic extract and enriched fraction can directly affect the redox state, and thus, prevents the embryotoxicity mediated by oxidative stress, in embryos of diabetic pregnancy.

Verbesina crocata: A pharmacognostic study for the treatment of wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbesina crocata (Cav.) Less. (Arnica or Capitaneja) is an endemic plant from Mexico restricted to the western part of the country. The aerial parts are used in traditional medicine for the treatment of wounds and burns. The objective of this investigation was to carry out a pharmacognostic study of V. crocata and establish markers that allow for the recognition of the characteristics of the plant and validate its traditional use. The study includes anatomical and chemical characteristics of the plant as well as evaluations of its antioxidant capacity and wound healing ability in a murine model. MATERIALS AND METHODS: An anatomical study of V. crocata was performed on the middle part of the leaf and stem. A methanolic extract of this species (VcME) was obtained by methanolic maceration of the aerial parts. Subsequently, a partition of the VcME was made to obtain a hexanic fraction (VcH). The phytochemical preliminary screening and characterization by high-performance liquid chromatography/mass spectrometry (HPLC-ESI/MS) of the VcME and VcH were performed. The antioxidant activity and total phenolic content were quantified. The wound healing capacity of the methanolic extract was determined in CD-1 mice by the healing rate, the tensiometric method, and histological analysis. RESULTS: The anatomical study of V. crocata showed the presence of two types of secretory structures and their position on the leaves. In addition, the characteristics of the middle vein and trichomes are potentially useful for recognition of the species. Chemical compounds detected by HPLC-ESI/MS reveal the presence of sitosterol glycoside and catechin derivatives as principal constituents of V. crocata. The VcME showed low antioxidant capacity and total phenolic. V. crocata had a similar healing effect to Recoveron® in the tensiometric method, but the rate of healing was higher. According to the histological analysis, the treatment of V. crocata promoted the remodelling phase 15 days after the incisional wound. CONCLUSION: This is the first pharmacognostic study of this species that covers the plant anatomy, chemical content and biological properties related to its traditional use. V. crocata favours wound healing according to physical and histological evaluations. In addition, the characteristics of the middle vein, trichomes and catechin glycosides are potentially useful for the recognition of this species.