Aquaporins in Sensory and Pain Transmission

Recent data suggest a possible involvement of Aquaporins (AQPs) in pain transmission. AQPs are small membrane channel proteins involved in osmoregulation and, to date, AQP1, AQP2, AQP3, AQP4, AQP5, AQP8 and AQP9 have been found in the nervous system. Nevertheless only AQP1, AQP2 and AQP4 seem to be involved in nociception

Bone Regeneration Using Mesenchymal Stromal Cells and Biocompatible Scaffolds: A Concise Review of the Current Clinical Trials

: Bone regenerative medicine is a clinical approach combining live osteoblast progenitors, such as mesenchymal stromal cells (MSCs), with a biocompatible scaffold that can integrate into host bone tissue and restore its structural integrity. Over the last few years, many tissue engineering strategies have been developed and thoroughly investigated; however, limited approaches have been translated to clinical application. Consequently, the development and clinical validation of regenerative approaches remain a centerpiece of investigational efforts towards the clinical translation of advanced bioengineered scaffolds. The aim of this review was to identify the latest clinical trials related to the use of scaffolds with or without MSCs to regenerate bone defects. A revision of the literature was performed in PubMed, Embase, and Clinicaltrials.gov from 2018 up to 2023. Nine clinical trials were analyzed according to the inclusion criteria: six presented in the literature and three reported in Clinicaltrials.gov. Data were extracted covering background trial information. Six of the clinical trials added cells to scaffolds, while three used scaffolds alone. The majority of scaffolds were composed of calcium phosphate ceramic alone, such as β-tricalcium phosphate (TCP) (two clinical trials), biphasic calcium phosphate bioceramic granules (three clinical trials), and anorganic bovine bone (two clinical trials), while bone marrow was the primary source of the MSCs (five clinical trials). The MSC expansion was performed in GMP facilities, using human platelet lysate (PL) as a supplement without osteogenic factors. Only one trial reported minor adverse events. Overall, these findings highlight the importance and efficacy of cell-scaffold constructs in regenerative medicine under different conditions. Despite the encouraging clinical results obtained, further studies are needed to assess their clinical efficacy in treating bone diseases to optimize their application

A comparison of melatonin and α-lipoic acid in the induction of antioxidant defences in L6 rat skeletal muscle cells.

Aging is characterized by a progressive deterioration in physiological functions and metabolic processes. The loss of cells during aging in vital tissues and organs is related to several factors including oxidative stress and inflammation. Skeletal muscle degeneration is common in elderly people; in fact, this tissue is particularly vulnerable to oxidative stress since it requires large amounts of oxygen, and thus, oxidative damage is abundant and accumulates with increasing age. Melatonin (N-acetyl-5-methoxytryptamine) is a highly efficient scavenger of reactive oxygen species and it also exhibits beneficial anti-inflammatory and anti-aging effects. This study investigated the susceptibility of rat L6 skeletal muscle cells to an induced oxidative stress following their exposure to hydrogen peroxide (50 μM) and evaluating the potential protective effects of pre-treatment with melatonin (10 nM) compared to the known beneficial effect of alpha-lipoic acid (300 μM). Hydrogen peroxide-induced obvious oxidative stress; it increased the expression of tumour necrosis factor-alpha and in turn promoted nuclear factor kappa-B and overrode the endogenous defence mechanisms. Conversely, pre-treatment of the hydrogen peroxide-exposed cells to melatonin or alpha-lipoic acid increased endogenous antioxidant enzymes, including superoxide dismutase-2 and heme oxygenase-1; moreover, they ameliorated significantly oxidative stress damage and partially reduced alterations in the muscle cells, which are typical of aging. In conclusion, melatonin was equally effective as alpha-lipoic acid; it exhibited marked antioxidant and anti-aging effects at the level of skeletal muscle in vitro even when it was given in a much lower dose than alpha-lipoic acid

Periodontitis Stage III–IV, Grade C and Correlated Factors: A Histomorphometric Study

Background: Periodontitis is a disease that leads to serious functional and esthetic dysfunctions. Periodontitis exists in different forms, and its etiology is related to multiple component causes. Two key processes involved in the evolution of this pathology are angiogenesis and inflammatory infiltrate. The aim of this study was to understand if important factors such as smoking, gender, age, plaque, pus, and probing pocket depth could influence the histomorphological pattern of generalized stage III-IV, grade C periodontitis (GPIII-IVC), which is a particular form of periodontitis. Methods: Eighteen subjects with GPIII-IVC were enrolled in this study. The percentage of inflammatory cells and the vascular area were measured and evaluated in relation to each periodontal disease-associated factor. Results: Females showed a significant increase in the percentage of inflammatory cells compared to males (6.29% vs. 2.28%, p-value = 0.020) and it was higher in non-smokers than in smokers (4.56% vs. 3.14%, p-value = 0.048). Young patients showed a significant increase in vascular area percentage compared to older patients (0.60% vs. 0.46%, p-value = 0.0006) and this percentage was also higher in non-smokers compared to smokers (0.41% vs. 0.55%, p-value = 0.0008). The vascular area was also more than halved in subjects with residual plaque on tooth surfaces (0.74% vs. 0.36%, p-value = 0.0005). Conclusions: These results suggested that even if these factors are commonly related to the worsening of periodontal status, some of them (pus and periodontal probing depth (PPD)) do not affect the inflammatory and vascular patterns

PENGARUH DOSIS PUPUK KOMPOS DAN NPK TERHADAP PERTUMBUHAN DAN HASIL BAWANG MERAH (ALLIUM ASCOLANICUM L.) VARIETAS BREBES

Penelitian ini bertujuan untuk mengetahui pengaruh kompos dan NPK pupuk terhadap pertumbuhan dan produksi tanaman bawang Brebes dan interaksi antara kedua faktor. Percobaan ini menggunakan Faktorial Rancangan Acak Pola. Faktor-faktor yang mempengaruhi dosis diuji kompos terdiri dari 4 tingkatan, yaitu: kontrol, 10, 20 dan 30 faktor ton / ha dan NPK dosis pupuk yang terdiri dari 4 tingkatan, yaitu: kontrol, 100, 200 dan 300 kg / ha, sehingga bahwa ada 16kombinasi perlakuan dengan 3 ulangan dan 48 unit percobaan, setiap unit terdiri dari 5 tanaman sampel percobaan.Hasil penelitian menunjukkan bahwa dosis kompos cenderung lebih baik pada dosis pengobatan 30 ton / ha untuk pertumbuhan dan hasil bawang. Sementara itu, NPK dosis pupuk untuk pertumbuhan dan hasil tanaman bawang merah cenderung lebih baik pada dosis pengobatan 200 kg NPK / ha. Tidak ada interaksi yang nyata antara perlakuan dosis pupuk NPK untuk kompos dengan semua variabel yang diamati pada pertumbuhan dan hasil bawang.Kata kunci: bawang, kompos, NPKBanda Ace

Aging of brain in hypercholesterolemic mice (ApoE -/-): melatonin receptor distribution

The protective role of melatonin has been investigated [1]. Some studies underlined its significant neuroprotective action with a role in aging processing. In patients with Alzheimer’s Disease, parallel to degenerative tissue changes, there was an overall decrease in the intensity of melatonin receptors in the pineal gland and occipital cortex [2]. Melatonin type 1 (MT1) and type 2 (MT2) receptors disclosed a quite widespread distribution in different brain regions. Recently our group demonstrated that an animal model of hypercholesterolemia, such as ApoE-/- mice, is more susceptible to developing severe liver injury, suggesting that in addition to vascular disease, increased cholesterol products and oxidative stress may also play a role in accelerating aging in the liver [3]. On the basis of this consideration, the aim of our work is to characterize the distribution of MT1 and MT2 in brain of ApoE -/- mice at different age (6 weeks, 16 weeks and 60 weeks) together with senescence markers using immunohistochemical technique to verify the role of these receptors in aging process. The results show an altered distribution of melatonin receptors and synaptic connectivity, indicating a process of aging in ApoE -/- mice and suggesting that melatonin treatment may represent a new approach to reduce brain aging and degeneration

H2O2 stress damage is reversed by melatonin in a spinal cord organotypic model

Spinal cord injury (SCI) is characterized to be a two-step process: the primary lesion consisting of the initial trauma; the secondary damage, characterized by multiple processes including inflammation, oxidative stress and cell death that lead to a significant expansion of the original damage and to an increase of the functional deficit (1). Among the aforementioned processes, the oxidative stress plays a significant role in pathophysiology of SCI. In this study, we evaluated the role of the melatonin, an indoleamine recognized as a potent antioxidant and immunomodulator (2, 3 )Reiter et al., 1995, Favero et al., 2015), on the oxidative stress, the tissue vitality and the neuritic plasticity in an experimental model of organotypic cultures of Sprague Dawley rat spinal cord slice (SPS) treated with hydrogen peroxide (H2O2) and/or melatonin. Five experimental protocols were performed: 1) control; 2) H2O2 exposure (50 μM); 3) melatonin treatment (5-10M for 24 hours); 4) H2O2 exposure and post-treatment with melatonin; 5) H2O2 exposure after pre-treatment with melatonin. Cellular death was investigated by propidium iodide (PI) assay and the vitality by MTT assay. The total thiols (SH) levels, contrasting the oxidative stress, the neuronal specific nuclear protein (NeuN) and the synaptophysin (Syp) immunopositivity were also evaluated. Melatonin significantly decreases the number of dead cells and increases slice vitality, mainly in slices treated before H2O2 exposure. Moreover, melatonin attenuates total thiols decrease and NeuN and Syp immunopositivity reduction. Overall, these findings suggest that melatonin may exert a potential beneficial effect upon the progression of SCI secondary damage, protecting the tissue from a further degeneration.This work was supported by grants from Giorgio Brunelli Foundation for Spinal Cord Injuries Research

Pineal gland and neuropathic pain

The pineal gland is a small neuroendocrine organ involved primarily in the circadian rhythm by the secretion of melatonin [1]. In addition, the pain modulatory properties of melatonin are generally recognized but its involvement in neuropathic pain regulation is not fully understood. In fact, it is known that the activation of the endogenous melatonin system in the spinal cord can reduce the generation, development and maintenance of central sensitization [2]. Moreover, melatonin showed an analgesic effect, in fact several works in animals [2] and in humans [3] underline its ability to inhibit hyperalgesia. In particular, intracerebroventricular and intraperitoneal melatonin, with its higher doses, produces a blockade of thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve. The aim of our work is to characterize the morphological changes in peripheral structures, such as plantar skin and dorsal root ganglia (DRG) of rats in a neuropathic pain model (chronic constriction injury) after a single melatonin treatment monitoring the behaviour and the changes in NO-system using immunohistochemical techniques. The behavioural results show an increase of withdrawal latency during plantar test already after 30 min from melatonin administration. The immunohistochemical results suggest that melatonin plays a crucial role in keratinocytes-mediated neuropathic pain transmission through the modulation of nitroxidergic system, which could have also a protective role at this site. In addition, at DRG level the NO-system is maintained at low level. These results suggest that melatonin administration or modulation of pineal gland activity may have clinical utility in neuropathic pain therapy in the future

Epithelial expression of vanilloid and cannabinoid receptors: a potential role in burning mouth syndrome pathogenesis

Burning mouth syndrome is an intraoral burning sensation in which the oral mucosa has a normal appearance and no medical or dental causes can be found. It remains an unknown disease for which long-term treatment is still lacking. The aim of this study is to assess in epithelial human tongue the expression of three receptors involved in pain transmission, such as a transient receptor potential vanilloid receptor type 1 (TRPV1) which mediates the sensation produced by chilli peppers, cannabinoid receptors type 1 (CB1) and type 2 (CB2), which are pathway-related to TRPV1. Epithelial cells express TRPV1, CB1 and CB2 receptors suggesting a role for these cells in sensory transduction. The study was performed on 8 healthy and 9 BMS patients. All patients underwent a 3-mm punch biopsy at the anterolateral aspect of the tongue close to the tip. Specimens were included in paraffin and serially cut to obtain 6um thick sections. The sections were processed for TRPV1, CB1 and CB2 immunohistochemistry. The analysis showed an altered expression of the studied receptors. In particular we observed an increase of TRPV1, a decrease of CB1 and an increase of CB2 expression in epithelial cells of the tongue with a change in morphological localization. So, these receptors seem to be correlated with BMS. These data could be useful for future characterization of BMS markers and specific therapies