Search

Autophagy is a self-degradative cellular process, involved in stress response such as starvation, hypoxia, and oxidative stress. This mechanism balances macro-molecule recycling to regulate cell homeostasis. In cancer, autophagy play a role in the development and progression, while several studies describe it as one of the key processes in drug resistance. In the last years, in addition to standard anti-cancer treatments such as chemotherapies and irradiation, targeted therapy became one of the most adopted strategies in clinical practices, mainly due to high specificity and reduced side effects. However, similar to standard treatments, drug resistance is the main challenge in most patients. Here, we summarize recent studies that investigated the role of autophagy in drug resistance after targeted therapy in different types of cancers. We highlight positive results and limitations of pre-clinical and clinical studies in which autophagy inhibitors are used in combination with targeted therapies., 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 © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Stem cells have the ability to rescue and/or repair injured tissue. In humans, it is possible to isolate different types of stem cells from the body. Among these, dental pulp stem cells (DPSCs) are relatively easily obtainable and exhibit high plasticity and multipotential capabilities. In particular they represent a gold standard for neural-crest-derived bone reconstruction in humans and can be used for the repair of body defects in low-risk autologous therapeutic strategies., Sources: An electronic search was conducted on PubMed databases and supplemented with a manual study of relevant references., Results: All research described in this review highlight that DPSCs are mesenchymal stem cells that could be used in clinical applications. Unfortunately, very few clinical trials have been reported. Major obstacles imposed on researchers are hindering the translation of potentially effective therapies to the clinic. Both researchers and regulatory institutions need to develop a new approach to this problem, drawing up a new policy for good manufacturing practice (GMP) procedures. We strongly suggest that only general rules be standardized rather than everything. Importantly, this would not have an effect on the safety of patients, but may very well affect the results, which cannot be identical for all patients, due to physiological diversity in the biology of each patient. Alternatively, it would be important to study the role of specific molecules that recruit endogenous stem cells for tissue regeneration. In this way, the clinical use of stem cells could be successfully developed., Conclusions: DPSCs are mesenchymal stem cells that differentiate into different tissues, maintain their characteristics after cryopreservation, differentiate into bone-like tissues when loaded on scaffolds in animal models, and regenerate bone in human grafts. In summary, all data reported up to now should encourage the development of clinical procedures using DPSCs., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bone defects are one of the most serious pathologies that need tissue regeneration therapies. Studies on mesenchymal stem cells are changing the way we treat bone diseases. MSCs have been used for the treatment of osteogenesis imperfecta, hypophosphatasia, osteonecrosis of the femoral head, osteoporosis, rheumatoid arthritis and osteoarthritis. In this context, it is becoming ever more clear that the future of therapies will be based on the use of stem cells. In this concise review, we highlight the importance of the use of MSCs in bone diseases, focusing on the role of histone deacetylases and Wnt pathways involved in osteogenesis. A better understanding of MSC biology and osteogenesis is needed in order to develop new and targeted therapeutic strategies for the treatment of bone diseases/disorders., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To investigate and compare the influence of surgical difficulty on postoperative pain after treatment of impacted mandibular third molars by rotatory osteotomy or Piezoelectric surgery., Materials and Methods: A prospective, randomized, split-mouth study was performed of 52 patients with bilateral and symmetrically oriented impacted mandibular third molars, who were surgically treated using a burr (Group A) on one random side of the lower jaw and a Piezoelectric device (Group B) on the contralateral side. Surgical difficulty was evaluated using a modified version of the Parant scale to categorize "simple extractions" and "complex extractions". Primary outcome parameters were the comparison of the postoperative pain evaluation rated on the Visual Analogue Scale from day 0 to day 6 postsurgery, and the assessment of differences in surgery time between the groups. Bone biopsies were taken during surgery to assess differences in bone tissue damage levels between the two different techniques., Results: In "complex extractions" lower pain evaluation and significantly shorter surgery times were recorded when rotatory instruments were used. In "simple extractions", similar surgery times were observed for both techniques, but pain was greatest on the day of surgery when the burr was used. Bone heat osteonecrosis was observed only in the rotatory group and a high level of alkaline phosphatase was noted only in the Piezoelectric group., Conclusion: Pain after extraction of a mandibular third molar increases with increased surgical difficulty and especially in longer interventions. The integrity of the bony structure observed after the ultrasonic technique may favour the bone healing process., (Copyright © 2012 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: Juvenile polyposis syndrome with gastric involvement may mimic Ménétrier's disease, which is correlated to transforming growth factor (TGF)α overproduction and PDX1 upregulation in the gastric fundus., Aim: We report a family with juvenile polyposis syndrome where one member showed typical features of Ménétrier's disease and concomitant Helicobacter pylori infection., Methods: We studied a 31-year-old woman belonging to a family with juvenile polyposis syndrome, who exhibited a particular form of hyperplastic gastropathy diagnosed as Ménétrier's disease with Helicobacter pylori infection., Results: TGFα overexpression and undetectable PDX1 expression were demonstrated in the fundic gastric biopsy specimens. In all affected members of the family we identified a 4-bp deletion in exon 9 of SMAD4 gene, a mutation usually associated with a more virulent form of juvenile polyposis syndrome with a higher incidence of gastric and colonic polyposis., Conclusion: To explain the association of juvenile polyposis syndrome with Ménétrier's disease we hypothesized a new mechanism that involves TGFβ-SMAD4 pathway inactivation and TGFα overexpression related to Helicobacter pylori infection., (Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The identity of biochemical players which underpin the commitment of CD34(+) hematopoietic stem cells to immunogenic or tolerogenic dendritic cells is largely unknown. To explore this issue, we employed a previously established cell-based system amenable to shift dendritic cell differentiation from the immunogenic into the tolerogenic pathway upon supplementation with a conventional cytokine cocktail containing thrombopoietin (TPO) and IL-16. We show that stringent regulation of cathepsins S and D, two proteases involved in antigen presentation, is crucial to engage cell commitment to either route. In response to TPO+IL-16-dependent signaling, both cathepsins undergo earlier maturation and down-regulation. Additionally, cystatin C orchestrates cathepsin S expression through a tight but reversible interaction that, based on a screen of adult stem cells from disparate origins, CD14(+) cells, primary fibroblasts and the MCF7 cell line, appears unique to CD34(+) stem cells from peripheral and cord blood. As shown by CD4(+) T cell proliferation in mixed-lymphocyte reactions, cell commitment to either pathway is disrupted upon cathepsin knockdown by RNAi. Surprisingly, similar effects were also observed upon gene overexpression, which prompts atypically accelerated maturation of cathepsins S and D in cells of the immunogenic pathway, similar to the tolerogenic route. Furthermore, RNAi studies revealed that cystatin C is a proteolytic target of cathepsin D and has a direct, causal impact on cell differentiation. Together, these findings uncover a novel biochemical cluster that is subject to time-controlled and rigorously balanced expression to mediate specific stem cell commitment at the crossroads towards tolerance or immunity., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Preventive (antioxidant activity) and chain-breaking (total peroxyl radical-trapping parameter) antioxidants in the serum of controls and butylated hydroxytoluene (BHT)-diet enriched nonobese diabetic (NOD) and C57B16/J mice from 5 to 25 weeks of age are measured in this study. A significant decrease in the overall potency of both antioxidant types is demonstrated in NOD untreated controls but not in animals whose diet was BHT-enriched. Therefore, we show that alterations of the antioxidant status in NOD mice is efficaciously counteracted by BHT.

Superoxide dismutase (SOD) levels, thought to be the first cellular defence against free radicals, were studied in the nonobese diabetesprone (NOD-p) mouse, an animal model of type 1 diabetes in which about 100% of females and 20% of males become diabetic. Nonobese diabetes nonprone (NON-p) mice were used as controls. Animals were followed from 5th to 22nd week of life. Results show that SOD levels in female NOD-p mice are extremely low. In males, values are considerably higher than in females but still lower than values found in control mice. Moreover, SOD levels did not significantly change with age, degree of insulitis or level of diabetes. Islet beta cells in this strain, therefore, seem to be poorly protected against the negative effects of free radicals and this may predispose to diabetes. Furthermore, alterations of SOD may not be directly related to the development of the disease as the enzyme's activity is not further modified with age or the progression of diabetes.

Diabetes produced spontaneously in the BB rat is similar to that observed in multiple low dose streptozocin-induced diabetes, both being characterized histologically by a lympho-monocytic infiltrate in the pancreatic islets (insulitis). Recent studies indicated that streptozocin acts through peroxidative patterns sensitive to superoxide dismutase (SOD) activity. We therefore conducted a time-course study to evaluate if SOD activity in the islets of Langerhans is related to the onset of diabetes in BB rats with varying degree of diabetes. It was found that SOD activity does not change with age nor with the onset of diabetes. However SOD activity in the islets of BB rats was significantly lower than in the control Wistars. This lower SOD activity may be a proneness factor that favors the development of the diabetic syndrome.

Eighty-five deciduous teeth, divided into five groups, were examined using a scanning electron microscope. The first two groups were etched for 60 and 120 sec respectively; the third and fourth groups were lightly milled and then etched for 60 and 120 sec respectively. In the first two groups, etching produced very few histological modifications. In the milled groups removal of the prismless enamel exposed the prisms to dissolution by the phosphoric acid. It was found that pretreatment and an etching time of 120 sec produced a constant and regularly distributed loss of inter- and intraprismatic substances.