The effects of combined and independent low-level laser and mesenchymal stem cell therapy on induced knee osteoarthritis: An animal study.

BACKGROUND: Mesenchymal stem cell (MSC) injection has emerged as a novel treatment for knee osteoarthritis (OA). In addition, low-level laser therapy (LLLT) has been reported to delay the progression of OA. Thus, the current study on animal models of OA investigated the effectiveness of these methods when administered independently and combined. METHODS: Twenty-five guinea pig models of OA were randomly sorted into five study groups. The test groups received intra-articular MSC, LLLT, and a combination of these therapeutics for 8 weeks. Radiological and histopathologic evaluations were carried out for the test groups and the control after the completion of treatments. RESULTS: The MSC-treated groups showed better outcomes in terms of all radiological and histological indexes compared with the control, apart from subchondral bone (P < 0.05). Similarly, but to a different extent, the LLLT-treated group showed better results than the controls (P < 0.05). The combination of MSC therapy and LLLT improved the cartilage, surface, matrix, space width, osteophytes, and radiologic OA scores more effectively than each of these methods alone (P < 0.05). CONCLUSIONS: According to our results, the combination of intra-articular MSC and LLLT can effectively improve OA in animal models. Further preclinical and clinical studies are recommended to assess the effectiveness of these therapeutics alone and in combination.

Involvement of Coenzyme Q10 in Various Neurodegenerative and Psychiatric Diseases.

Coenzyme Q10 (CoQ10), commonly known as ubiquinone, is a vitamin-like component generated in mitochondrial inner membranes. This molecule is detected broadly in different parts of the human body in various quantities. This molecule can be absorbed by the digestive system from various nutritional sources as supplements. CoQ10 exists in three states: in a of reduced form (ubiquinol), in a semiquinone radical form, and in oxidized ubiquinone form in different organs of the body, playing a crucial role in electron transportation and contributing to energy metabolism and oxygen utilization, especially in the musculoskeletal and nervous systems. Since the early 1980s, research about CoQ10 has become the interest for two reasons. First, CoQ10 deficiency has been found to have a link with cardiovascular, neurologic, and cancer disorders. Second, this molecule has an antioxidant and free-radical scavenger nature. Since then, several investigations have indicated that the drug may benefit patients with cardiovascular, neuromuscular, and neurodegenerative illnesses. CoQ10 may protect the neurological system from degeneration and degradation due to its antioxidant and energy-regulating activity in mitochondria. This agent has shown its efficacy in preventing and treating neurological diseases such as migraine, Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, and Friedreich's ataxia. This study reviews the literature to highlight this agent's potential therapeutic effects in the mentioned neurological disorders.

Nanoliposomal peptides derived from Spirulina platensis protein accelerate full-thickness wound healing.

Spirulina platensis is a type of blue-green algae that contains large amounts of protein with therapeutic effects. The present study was performed to investigate the effects of encapsulated Spirulina protein hydrolysates (SPH) with nanoliposomes (NLPs) in reducing wound healing period. SPH-loaded NLPs showed the size and zeta potential of 158 nm and -48 mV, respectively; as well as a uniform non-aggregated morphology. In-vitro MTT toxicity studies on the Human Foreskin Fibroblast (HFFF-2) cell line exhibited that the hydrolyzed peptides had no toxic effect and increased cell growth. The scratch test confirmed the MTT results. For in-vivo study, 162 mice were divided into nine groups, including the mice groups treated with blank gel, blank NLPs, and those treated with 2.5, 5, and 10 % SPH and SPH-loaded NLPs. The histopathological assessment was done to investigate rate of fibroblast proliferation and epithelialization. Immunofluorescence staining for bFGF, CD31, COL1A was conducted. The results showed that the mice group treated with SPH-NLPs showed higher wound contraction, epithelization, fibroblast proliferation, and higher expressions for bFGF, CD31, COL1A compared with blanks and other groups. In conclusion, the derived and encapsulated peptides showed significant effects in accelerating wound healing via angiogenesis and collagen production.

Short-term Follow-up of Patients Receiving Bio-integrative Screws for Lisfranc Injuries: A Case Series.

Introduction: Various methods are used for open reduction and internal fixation of Lisfranc injuries, and each shows different post-treatment outcomes. Other than the common post-surgery problems in these patients, including possible non-anatomical reduction, implant loosening, breakage, and arthritis, most of these patients will undergo a second surgery for implant removal which itself might cause further complications. To reduce the need for re-operation, bio-degradable or bio-integrative implants can be promising; however, the short- and long-term outcomes have been scarcely investigated to date. Case Report: We followed up 10 adult patients who received bio-integrative screws for Lisfranc injuries. The patients were asked to fill out the patient-reported outcome measures (PROMs) surveys during one of the follow-up visits. We gathered variables including the type of injury, pain score, and PROMs including physical function (PF), pain interference, pain intensity, and depression. We evaluated the patients for wound dehiscence, non-union, and hardware failure. The median (interquartile range [IQR]) follow-up time of the patients in this study was 9 (4-11.5) months. Nine out of 10 patients with Lisfranc injuries who received bio-integrative screws showed improvements in their pain scores and started progressive weight-bearing. Among 3 patients who had sport-related Lisfranc injuries, 2 returned to play in <6 months, and one started side-to-side agility work in <3 months. The median (IQR) scores of PROMs representing PF, depression, physical health, mental health, pain interference, and pain intensity were 49.5 (30.1-61.9), 41 (41-49), 50.8 (39.2-57.7), 59 (48.9-63.7), 51.7 (41.6-72.6), and 43.5 (37.8-55.2), respectively. Conclusion: Our results demonstrated promising short-term outcomes of using bio-integrative screws in patients with Lisfranc injuries based on PROMs and the rate of complications. Future studies on larger populations and more comprehensive variables with longer follow-up duration should be the next step in evaluating the pros and cons of these new implants.

Nano-liposomal zein hydrolysate for improved apoptotic activity and therapeutic index in lung cancer treatment.

Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC50 value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.

Therapeutic effects of stem cells in different body systems, a novel method that is yet to gain trust: A comprehensive review.

Stem cell therapy has been used to treat several types of diseases, and it is expected that its therapeutic uses shall increase as novel lines of evidence begin to appear. Furthermore, stem cells have the potential to make new tissues and organs. Thus, some scientists propose that organ transplantation will significantly rely on stem cell technology and organogenesis in the future. Stem cells and its robust potential to differentiate into specific types of cells and regenerate tissues and body organs, have been investigated by numerous clinician scientists and researchers for their therapeutic effects. Degenerative diseases in different organs have been the main target of stem cell therapy. Neurodegenerative diseases such as Alzheimer's, musculoskeletal diseases such as osteoarthritis, congenital cardiovascular diseases, and blood cell diseases such as leukemia are among the health conditions that have benefited from stem cell therapy advancements. One of the most challenging parts of the process of incorporating stem cells into clinical practice is controlling their division and differentiation potentials. Sometimes, their potential for  uncontrolled growth will make these cells tumorigenic. Another caveat in this process is the ability to control the differentiation process. While stem cells can easily differentiate into a wide variety of cells,  a paracrine effect controlled activity, being in an appropriate medium will cause abnormal differentiation leading to treatment failure. In this review, we aim to provide an overview of the therapeutic effects of stem cells in diseases of various organ systems. In order to advance this new treatment to its full potential, researchers should focus on establishing methods to control the differentiation process, while policymakers should take an active role in providing adequate facilities and equipment for these projects. Large population clinical trials are a necessary tool that will help build trust in this method. Moreover, improving social awareness about the advantages and adverse effects of stem cell therapy is required to develop a rational demand in the society, and consequently, healthcare systems should consider established stem cell-based therapeutic methods in their treatment algorithms.

Analysis of hard tissue facial symmetry after unilateral mandibular reconstruction.

BACKGROUND: This study aimed to determine how successful reconstruction of the mandible can recover the symmetry. MATERIALS AND METHODS: All patients who underwent surgical treatment for unilateral mandibular reconstruction in 4 years were retrospectively examined. Bilateral differences of gonion (GO) positions were measured in 3 dimensions based on immediate postoperative computed tomography. The data collected was analyzed in 3 ways: First, the comparison of bilateral differences of GO in 3 dimensions. Second, the mean Asymmetry Index in control subjects was used to divide all cases into three groups: "Symmetry," "Asymmetry," and "Marked asymmetry." Third, "maximum normal asymmetry" was calculated, and all cases were categorized as below and above maximum normal asymmetry. The difference between two gonial angles was used to determine the amount of asymmetry. RESULTS: Forty-seven patients and 47 normal adults were enrolled. The mean bilateral GO difference in the control group was higher than in the study group patients, but it was not statistically significant. The mean Asymmetry Index for the control group was not also significantly higher than the study cases. The study group was "Symmetric" in 78.7% of the cases whereas the control group in 91.4%, 19.1% of the study group and 8.5% of controls were "Asymmetric," and 2.1% of study cases and 0% of controls were "Markedly Asymmetric." Maximum normal asymmetry was 82.9% in the study group and 97.8% in the control group. The mean differences between the right and left gonial angles were higher in the study group, but it was not significant (P = 0.1). CONCLUSIONS: Our study's results showed that bilateral symmetry in mandibular reconstruction patients was satisfactory and similar to the normal individuals.

Significance of E-cadherin and Vimentin as epithelial-mesenchymal transition markers in colorectal carcinoma prognosis.

Colorectal cancer is the most common malignancy of the gastrointestinal tract with very high mortality. One of the most distinguishing features for the establishment of an epithelial-mesenchymal transition phenotype is the alteration of mesenchymal markers and structural adhesion proteins. We investigated the level of Vimentin and E-cadherin expression in relation to invasion and metastasis on colorectal cancer patients. Tissue specimens were collected consecutively from thirty-nine colorectal carcinoma patients during surgeries. The patients were diagnosed and treated between 2013 and 2016. In order to histological staging, tissue sections were prepared from formalin-fixed paraffin-embedded blocks and stained with Hematoxylin and Eosin. Also for evaluating the epithelial-mesenchymal transition markers, E-cadherin and Vimentin, all patient samples were stained and detected via immunohistochemistry, and afterwards the results were analyzed to determine whether these markers could be useful prognostic markers for predicting colorectal cancer patient outcomes. The expression of Vimentin as a mesenchymal marker along with rising grade of cancer, pathological stages, and metastasis to regional lymph nodes increased furthermore, in cancers with vascular invasion, Vimentin value was high. Reversely, the expression of E-cadherin with climbing grade, stages and colon cancer categories decreased and also in cancers with vascular invasion reduced. Variation of the markers had no relation to age and sex. In summary, along with cancer progression level of Vimentin expression varies inversely with E-cadherin expression and by increasing metastasis and invasion the Vimentin expression elevates. Further evaluation in this area might lead to a good method for predicting progressive clone cancer.

Anti-invasive and antiproliferative effects of Pleurotus ostreatus extract on acute leukemia cell lines.

BACKGROUND: Currently, mushrooms have been used in traditional and folk medicines for their therapeutic activities, such as antibiotic, antitumor, anti-inflammatory, anticancer, antileukemic and immunomodulatory actions. This investigation evaluates the anti-invasive, antiproliferative and cytotoxic effects of Pleurotus ostreatus (Pleurotaceae) on leukemia cell lines. METHODS: The proliferation of KG-1 cells was measured by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay after treatment with gradient dilutions of P. ostreatus extract. Then, the minimum inhibitory concentration (MIC) of the extract was determined. Moreover, the proliferation of Jurkat cells and bone marrow mesenchymal stem cells (BMSCs), a cancerous cell line and normal body cells, respectively, was considered. The apoptotic morphology of treated KG-1 cells was evaluated with Giemsa staining. The invasion and migration of cells were evaluated using transwell invasion assay. Thereafter, the rates of apoptosis and necrosis were measured by using flow cytometry, and BAX and MMP-9 gene expression were evaluated using quantitative reverse transcription-polymerase chain reaction as apoptotic and metastatic genes, respectively. RESULTS: The MIC of the extract was determined to be 1 mg/mL after 48 h. According to the results, the extract decreased the proliferation of leukemia cell lines (KG-1 and Jurkat cells) but had no antiproliferative effects on BMSCs. Moreover, KG-1 cell migration and MMP-9 gene expression decreased after the treatment, and the rate of apoptosis and BAX gene expression increased significantly. CONCLUSIONS: According to the efficient therapeutic properties of P. ostreatus on leukemia cell lines, this mushroom could be introduced as a natural medicine to cure leukemic patients who suffer from the harmful side effects and enormous costs of chemotherapy.

Comparison of anticancer effect of Pleurotus ostreatus extract with doxorubicin hydrochloride alone and plus thermotherapy on erythroleukemia cell line.

Background Recent studies have introduced Pleurotus ostreatus (Pleurotaceae) as a herbal medicine for treating different types of cancer. This survey utilizes P. ostreatus and doxorubicin hydrochloride (DOX) alone and then with hyperthermia to investigate the erythroleukemia cell line. This study evaluates and compares the apoptotic and necrotic effects of various treatments on the KG-1 cell line. Methods The proliferation of KG-1 cells was measured by using a tetrazolium salt (MTT)-based colorimetric assay during 96 h after treatment by gradient dilutions of 100 ng/mL to 100 mg/mL of P. ostreatus methanol extract and then the minimum inhibitory concentration (MIC) was determined and was applied in additional experiments. Afterward, the cells were treated using P. ostreatus extract, DOX (6.95 mg/L), and hyperthermia (42 and 44 °C), separately and then applying hyperthermia. Finally, the ratios of apoptosis and necrosis after 24 h incubation were evaluated by using flow cytometry. Results The MIC of the extract was determined (1 mg/mL), which significantly increased the ratio of apoptosis rather than necrosis, whereas the DOX treatment primarily induced necrosis on the KG-1 cells. The anticancer effects of the mushroom extract were significantly increased when it was combined with thermotherapy, which exhibited apoptotic effects at 42 °C but induced necrosis at 44 °C. Conclusions The results suggest that P. ostreatus extract induces apoptosis on KG-1 cells and its anticancer effects are significantly increased in combination with thermotherapy. Therefore, P. ostreatus could be considered as an alternative with anticancer effect for further studies in erythroleukemia patients.

The association of vimentin and fibronectin gene expression with epithelial-mesenchymal transition and tumor malignancy in colorectal carcinoma.

Colorectal cancer is the most common malignancy of the gastrointestinal tract with very high mortality. One of the most distinguishing features for the establishment of an epithelial-mesenchymal transition phenotype is the alteration of mesenchymal markers expression and structural adhesion proteins. We evaluated the significance of vimentin and fibronectin gene expression in relation to invasion and metastasis in CRC patients. Tissue specimens were collected consecutively from forty-five colorectal carcinoma patients during surgeries. Tissues were divided into two separate parts for pathological and molecular assays. In order to histological staging, tissue sections were prepared from formalin-fixed paraffin-embedded blocks and stained with Hematoxylin and Eosin. To quantify gene expression, specimens were dissected and homogenized. Moreover, SW480, SW48, SW948, Caco-2, HT-29 and LS174T as human colon cancer cell lines were obtained and cultured, then molecular analyzing was performed. As results the expression of VIM gene increased in SW480, SW48 and SW948 while it decreased in Caco-2, HT-29 and LS174T. Moreover, FN was up-regulated in Caco-2, HT-29 and SW948, while it was down-regulated in SW480, SW48 and LS174T. In tissues, vimentin and fibronectin expression significantly increased in stromal cells, whereas vimentin decreased in colonic epithelial cells and fibronectin had no significant change. Vimentin and fibronectin expression were changed in tumor tissues. It was found an association between vimentin expression with age and tumor size; over-expression in older age and decreasing in larger tumor size. Furthermore, fibronectin over-expression is correlated to older age and high tumor stages; up-regulation with increasing age and high tumor stages.