The Application of Mesenchymal Stromal Cells and Their Homing Capabilities to Regenerate the Intervertebral Disc

Chronic low back pain (LBP) remains a challenging condition to treat, and especially to cure. If conservative treatment approaches fail, the current “gold standard” for intervertebral disc degeneration (IDD)-provoked back pain is spinal fusion. However, due to its invasive and destructive nature, the focus of orthopedic research related to the intervertebral disc (IVD) has shifted more towards cell-based therapeutic approaches. They aim to reduce or even reverse the degenerative cascade by mimicking the human body’s physiological healing system. The implementation of progenitor and/or stem cells and, in particular, the delivery of mesenchymal stromal cells (MSCs) has revealed significant potential to cure the degenerated/injured IVD. Over the past decade, many research groups have invested efforts to find ways to utilize these cells as efficiently and sustainably as possible. This narrative literature review presents a summary of achievements made with the application of MSCs for the regeneration of the IVD in recent years, including their preclinical and clinical applications. Moreover, this review presents state-of-the-art strategies on how the homing capabilities of MSCs can be utilized to repair damaged or degenerated IVDs, as well as their current limitations and future perspectives.     

Genotypic Variation under Fe Deficiency Results in Rapid Changes in Protein Expressions and Genes Involved in Fe Metabolism and Antioxidant Mechanisms in Tomato Seedlings (Solanum lycopersicum L.)

To investigate Fe deficiency tolerance in tomato cultivars, quantification of proteins and genes involved in Fe metabolism and antioxidant mechanisms were performed in “Roggusanmaru” and “Super Doterang”. Fe deficiency (Moderate, low and –Fe) significantly decreased the biomass, total, and apoplastic Fe concentration of “Roggusanmaru”, while a slight variation was observed in “Super Doterang” cultivar. The quantity of important photosynthetic pigments such as total chlorophyll and carotenoid contents significantly decreased in “Roggusanmaru” than “Super Doterang” cultivar. The total protein profile in leaves and roots determines that “Super Doterang” exhibited an optimal tolerance to Fe deficiency compared to “Roggusanmaru” cultivar. A reduction in expression of PSI (photosystem I), PSII (photosystem II) super-complexes and related thylakoid protein contents were detected in “Roggusanmaru” than “Super Doterang” cultivar. Moreover, the relative gene expression of SlPSI and SlPSII were well maintained in “Super Doterang” than “Roggusanmaru” cultivar. The relative expression of genes involved in Fe-transport (SlIRT1 and SlIRT2) and Fe(III) chelates reductase oxidase (SlFRO1) were relatively reduced in “Roggusanmaru”, while increased in “Super Doterang” cultivar under Fe deficient conditions. The H⁺-ATPase relative gene expression (SlAHA1) in roots were maintained in “Super Doterang” compared to “Roggusanmaru”. Furthermore, the gene expressions involved in antioxidant defense mechanisms (SlSOD, SlAPX and SlCAT) in leaves and roots showed that these genes were highly increased in “Super Doterang”, whereas decreased in “Roggusanmaru” cultivar under Fe deficiency. The present study suggested that “Super Doterang” is better tomato cultivar than “Roggusanmaru” for calcareous soils.     

Intervertebral Disc and Adipokine Leptin—Loves Me,Loves Me Not

Leptin—the most famous adipose tissue-secreted hormone—in the human body is mostly observed in a negative connotation, as the hormone level increases with the accumulation of body fat. Nowadays, fatness is becoming another normal body shape. Fatness is burdened with numerous illnesses—including low back pain and degenerative disease of lumbar intervertebral disc (IVD). IVD degeneration and IVD inflammation are two indiscerptible phenomena. Irrespective of the underlying pathophysiological background (trauma, obesity, nutrient deficiency), the inflammation is crucial in triggering IVD degeneration. Leptin is usually depicted as a proinflammatory adipokine. Many studies aimed at explaining the role of leptin in IVD degeneration, though mostly in in vitro and on animal models, confirmed leptin’s “bad reputation”. However, several studies found that leptin might have protective role in IVD metabolism. This review examines the current literature on the metabolic role of different depots of adipose tissue, with focus on leptin, in pathogenesis of IVD degeneration.     

Impact of Four Ovine TMEM154 Haplotypes on Ewes during Multiyear Lentivirus Exposure

Polypeptide variation encoded by the ovine transmembrane protein 154 gene (TMEM154) is associated with susceptibility to ovine lentivirus, the causative agent of Ovine Progressive Pneumonia (OPP) and Visna/Maedi. Our aim was to compare the four most prevalent TMEM154 haplotypes on the incidence of infection and ewe productivity during natural multiyear virus exposure. Prospective cohort studies were designed to test gene action and estimate effects of TMEM154 haplotypes encoding distinctive variant residues: K35 (“1”), I70 (“2”), ancestral (“3”), and A4del/M44 (“4”). Exposure consisted of co-mingling infected ewes at a rate greater than 30% with serological status evaluated every four months. For ewes with one or two copies of the highly susceptible haplotypes “2” and ”3”, the infection prevalence steadily increased to nearly 100% at 55 months. Haplotypes “2” and “3” were equally susceptible and dominant to haplotype “1”. A difference was not detected (p < 0.53) in the magnitude of effect with haplotype combinations of “1” and ”4”. The ewe infection prevalence with “1,1”; “1,4”; and “4,4” was 10% to 40% at 55 months. The latter suggested that two copies of the K35 amino acid substitution (“1”) were as effective as a homozygous TMEM154 “knockout” with the frame-shift deletion mutation (“4”) in reducing infection susceptibility. When considering ewe reproductive performance, a difference was not detected when comparing haplotypes “2”, and “3” to each other, or “1” and “4” to each other. Our study indicated that ewes with two copies of the severely truncated versions of TMEM154 (“4,4”) had normal lamb productivity. Without complete understanding of the natural function of TMEM154 our recommendations to producers interested in using TMEM154 selection to reduce their flock’s genetic predisposition to OPP are encouraged to increase the frequency of TMEM154 haplotype K35 (“1”) since it encodes a full-length protein with minimal difference to the ancestral polypeptide.     

Insulin-Like Peptide Receptor-Mediated Signaling Pathways Orchestrate Regulation of Growth in the Pacific Oyster (Crassostrea gigas), as Revealed by Gene Expression Profiles

The involvement of insulin/insulin-like growth factor signaling (IIS) pathways in the growth regulation of marine invertebrates remains largely unexplored. In this study, we used a fast-growing Pacific oyster (Crassostrea gigas) variety “Haida No.1” as the material with which to unravel the role of IIS systems in growth regulation in oysters. Systematic bioinformatics analyses allowed us to identify major components of the IIS signaling pathway and insulin-like peptide receptor (ILPR)-mediated signaling pathways, including PI3K-AKT, RAS-MAPK, and TOR, in C. gigas. The expression levels of the major genes in IIS and its downstream signaling pathways were significantly higher in “Haida No.1” than in wild oysters, suggesting their involvement in the growth regulation of C. gigas. The expression profiles of IIS and its downstream signaling pathway genes were significantly altered by nutrient abundance and culture temperature. These results suggest that the IIS signaling pathway coupled with the ILPR-mediated signaling pathways orchestrate the regulation of energy metabolism to control growth in Pacific oysters.     

The Effects of Exercise Training on Mitochondrial Function in Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I² = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.     

Secondary Metabolic Profile as a Tool for Distinction and Characterization of Cultivars of Black Pepper (Piper nigrum L.) Cultivated in Pará State,Brazil

This study evaluated the chemical compositions of the leaves and fruits of eight black pepper cultivars cultivated in Pará State (Amazon, Brazil). Hydrodistillation and gas chromatography–mass spectrometry were employed to extract and analyze the volatile compounds, respectively. Sesquiterpene hydrocarbons were predominant (58.5–90.9%) in the cultivars “Cingapura”, “Equador”, “Guajarina”, “Iaçará”, and “Kottanadan”, and “Bragantina”, “Clonada”, and “Uthirankota” displayed oxygenated sesquiterpenoids (50.6–75.0%). The multivariate statistical analysis applied using volatile composition grouped the samples into four groups: γ-Elemene, curzerene, and δ-elemene (“Equador”/“Guajarina”, I); δ-elemene (“Iaçará”/“Kottanadan”/“Cingapura”, II); elemol (“Clonada”/“Uthirankota”, III) and α-muurolol, bicyclogermacrene, and cubebol (“Bragantina”, IV). The major compounds in all fruit samples were monoterpene hydrocarbons such as α-pinene, β-pinene, and limonene. Among the cultivar leaves, phenolics content (44.75–140.53 mg GAE·g⁻¹ FW), the enzymatic activity of phenylalanine-ammonia lyase (20.19–57.22 µU·mL⁻¹), and carotenoids (0.21–2.31 µg·mL⁻¹) displayed significant variations. Due to black pepper’s susceptibility to Fusarium infection, a molecular docking analysis was carried out on Fusarium protein targets using each cultivar’s volatile components. F. oxysporum endoglucanase was identified as the preferential protein target of the compounds. These results can be used to identify chemical markers related to the susceptibility degree of black pepper cultivars to plant diseases prevalent in Pará State.     

Antioxidant Enzymatic Activities and Gene Expression Associated with Heat Tolerance in the Stems and Roots of Two Cucurbit Species (“Cucurbita maxima” and “Cucurbita moschata”) and Their Interspecific Inbred Line “Maxchata”

The elucidation of heat tolerance mechanisms is required to combat the challenges of global warming. This study aimed to determine the antioxidant enzyme responses to heat stress, at the enzymatic activity and gene expression levels, and to investigate the antioxidative alterations associated with heat tolerance in the stems and roots of squashes using three genotypes differing in heat tolerance. Plants of heat-tolerant “C. moschata”, thermolabile “C. maxima” and moderately heat-tolerant interspecific inbred line “Maxchata” genotypes were exposed to moderate (37 °C) and severe (42 °C) heat shocks. “C. moschata” exhibited comparatively little oxidative damage, with the lowest hydrogen peroxide (H₂O₂), superoxide (O₂⁻) and malondialdehyde (MDA) contents in the roots compared to stems, followed by “Maxchata”. The enzyme activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and peroxidase (POD) were found to be increased with heat stress in tolerant genotypes. The significant inductions of FeSOD, MnSOD, APX2, CAT1 and CAT3 isoforms in tolerant genotypes suggested their participation in heat tolerance. The differential isoform patterns of SOD, APX and CAT between stems and roots also indicated their tissue specificity. Furthermore, despite the sequence similarity of the studied antioxidant genes among “C. maxima” and “Maxchata”, most of these genes were highly induced under heat stress in “Maxchata”, which contributed to its heat tolerance. This phenomenon also indicated the involvement of other unknown genetic and/or epigenetic factors in controlling the expression of these antioxidant genes in squashes, which demands further exploration.     

Foliar Silicon Spray before Summer Cutting Propagation Enhances Resistance to Powdery Mildew of Daughter Plants

Silicon (Si) has beneficial effects on not only plant growth but also against biotic and abiotic stresses. However, a few studies focus on how Si application helps strawberry (Fragaria × ananassa Duch.) resist powdery mildew. The aim of this work was to find out the optimal Si application method before cutting propagation to enhance the resistance to powdery mildew in strawberry “daughter” plants. Naturally infected “mother” plants of ‘Sulhyang’, ‘Maehyang’, and ‘Kuemsil’ strawberries were supplied with Si. Potassium silicate (K₂SiO₃) at a final concentration of 75 mg·L⁻¹ Si was either added to the medium for drenching or sprayed to the leaves of the “mother” or “daughter” plant, or soluble Si fertilizer was used to dress the “mother” plant. The Si application significantly increased the shoot fresh weight of the “daughter” plants. Supplemental Si also increased the contents of phosphorus (P), potassium (K), and magnesium (Mg). In addition, the Si treatment decreased the damage of powdery mildew by increased level of proline content and suppressive reactive oxygen species. After applying Si, the length and density of hyphae on the leaf surface decreased. In addition, the infected area of “daughter” plant leaves covered with powdery mildew decreased. This study also demonstrated that Si increased the expression of resistance-gene and decreased the expression of susceptibility-gene of strawberry. Overall, Si application promoted the growth of the “daughter” plants regardless of the application method. Direct foliar Si spray to the “daughter” plants before cutting propagation is recommended to increase their resistance to powdery mildew.     

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Cumulative evidence has pointed out cannabinoid CB2 receptors (CB₂r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB₂r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles. The search strategy was as follows: “Receptor, Cannabinoid, CB2” AND “Alcohol-Related Disorders” AND “human/or patients”; “Receptor, Cannabinoid, CB2” AND “Alcohol” OR “Ethanol” AND “rodents/or mice/or rats”. Pharmacological approaches demonstrated that the activation or blockade of CB₂r modulated different alcohol-addictive behaviors. Rodent models of alcoholism revealed significant alterations of CB₂r in brain areas of the reward system. In addition, mice lacking CB₂r (CB₂KO) show increased alcohol consumption, motivation, and relapse alterations. It has been stressed that the potential neurobiological mechanisms underlying their behavioral effects involve critical elements of the alcohol reward system. Interestingly, recent postmortem studies showed CNR2 alterations in brain areas of alcoholic patients. Moreover, although the number of studies is limited, the results revealed an association between some genetic alterations of the CNR2 and an increased risk for developing AUD. This review provides evidence that CB₂r may play a role in alcohol addiction. Clinical studies are necessary to figure out whether CB₂r ligands may prove useful for the treatment of AUD in humans.     

Development of a Method for Producing oxLDL: Characterization of Their Effects on HPV-Positive Head and Neck Cancer Cells

Cardiovascular diseases (CVD) and cancers are the two main causes of death worldwide. The initiation and progression of atherosclerosis is, in large part, caused by oxidized low-density lipoproteins (oxLDL); interestingly, oxLDL may also play a role in cancer cell metabolism and migration. As oxLDL are generally obtained by tedious ultracentrifugation procedures, “home-made” oxLDL were obtained by (i) applying a purification kit to isolate LDL and VLDL from human plasma; (ii) isolating LDL from VLDL by gel permeation chromatography (GPC); and (iii) oxidating LDL through CuSO₄ incubation. On three HPV-positive head and neck cancer cells (HNCC) (93VU-147T, UM-SCC47, and UPCI-SCC154), cell migration was assessed using Boyden chambers, the Wnt/ß-catenin pathway was analyzed by Western Blotting, and the expression of two oxLDL receptors, LOX-1 and CD36, in response to oxLDL exposure, was analysed by immunofluorescence. Our data indicate: (a) a non-significant difference between reference and “home-made” oxLDL; (b) a decreased migration, parallel to an inhibition of the ß-catenin pathway; and (c) an increase of CD36 and LOX-1 expression in all HNCC. In conclusion, we successfully produced oxLDL. Our results demonstrate a decrease in HNCC migration after oxLDL exposure, and an increased expression of LOX-1 and CD36 associated with lipid uptake.