Effect of stem cell secretome in skin rejuvenation: a narrative review.

PURPOSE: Cutaneous aging is an inevitable biological process that develops over time due to cumulative cellular and molecular changes caused by exposure to intrinsic (chronological aging) and extrinsic (photo-aging) factors on the skin. Skin aging is characterized by a decline in the body's capability to sustain senescence, dermal cell apoptosis, and homeostasis. Stem cell secretions (secretome) are defined as the total set of dynamically overlapping paracrine soluble growth factors, cytokines, chemokines, angiogenic factors, extracellular matrix proteins, and antimicrobial peptides known to be responsible for tissue rejuvenation, regeneration, homeostasis, and immunomodulation. METHODS: In this review, we summarized the molecular and regulatory mechanism of the secretome in preventing the skin aging process, as well as its capacity in inducing skin rejuvenation. Furthermore, we illustrated secretome efficiency as an anti-aging therapeutic strategy based on in vitro and in vivo published studies. RESULTS: In all reviewed publications, the secretome has been proven to be the most effective treatment for aged skin, capable of reversing the aging process through the action of cytokines, growth factors, and collagen, which are its primary components. The reported mechanism of action involves modulating the signaling pathways of aging and replenishing the skin with collagen, fibronectin, and elastin, ultimately resulting in skin renewal and rejuvenation. CONCLUSION: In conclusion, compared to available treatments, the secretome shows great promise as an anti-aging therapy.

Stem cell secretome as a mechanism for restoring hair loss due to stress, particularly alopecia areata: narrative review.

BACKGROUND: Living organisms are continuously exposed to multiple internal and external stimuli which may influence their emotional, psychological, and physical behaviors. Stress can modify brain structures, reduces functional memory and results in many diseases such as skin disorders like acne, psoriasis, telogen effluvium, and alopecia areata. In this review, we aim to discuss the effect of secretome on treating alopecia, especially alopecia areata. We will shed the light on the mechanism of action of the secretome in the recovery of hair loss and this by reviewing all reported in vitro and in vivo literature. MAIN BODY: Hair loss has been widely known to be enhanced by stressful events. Alopecia areata is one of the skin disorders which can be highly induced by neurogenic stress especially if the patient has a predisposed genetic background. This condition is an autoimmune disease where stress in this case activates the immune response to attack the body itself leading to hair cycle destruction. The currently available treatments include medicines, laser therapy, phototherapy, and alternative medicine therapies with little or no satisfactory results. Regenerative medicine is a new era in medicine showing promising results in treating many medical conditions including Alopecia. The therapeutic effects of stem cells are due to their paracrine and trophic effects which are due to their secretions (secretome). CONCLUSION: Stem cells should be more used as an alternative to conventional  therapies due to their positive outcomes. More clinical trials on humans should be done to maximize the dose needed and type of stem cells that must be used to treat alopecia areata.

MicroRNA-143 as a new weapon against cancer: overview of the mechanistic insights and long non-coding RNA mediated regulation of miRNA-143 in different cancers.

Central dogma of molecular biology, a term coined by Francis Crick in 1958 was considered to be the cornerstone of molecular biology unless molecular biologists challenged the idea after ground-breaking discovery of non-coding RNAs. Discovery of microRNAs marked a new era and revolutionized our understanding related to puzzling mysteries about intermediate steps between transcription and translation. Technological advancements have spawned a multitude of platforms for profiling of long-noncoding RNAs and miRNAs in different cancers. Detailed investigation of mRNA targets of miRNAs has enabled high-order analyses of interconnected networks and revealed affected pathways in different cancers. miR-143 has emerged as a multi-talented tumor suppressor microRNA having considerable ability to inhibit and prevent cancer via regulation of myriad of oncogenes. In this review, we will summarize most recent evidence related to characteristically unique ability of miR-143 to target different oncogenic mRNAs in different cancers. We will also comprehensively discuss how scientists have identified multiple long non-coding RNAs reportedly involved in promoting the expression of oncogenes by interfering with miR-143 mediated targeting of these oncogenes. Because of excellent ability of miR-143 to effectively target oncogenic mRNAs, researchers have started to focus on use of miR-143 mimics to restore expression of miR-143 in various cancers.

Different TP53 mutants in p53 overexpressed epithelial ovarian carcinoma can be associated both with altered and unaltered glycolytic and apoptotic profiles.

BACKGROUND: p53 is a tumor suppressor and key regulator of glycolysis in cancer cells, however highly mutated in tumors. In ovarian cancer, studies concerning p53 mutations focus on the DNA binding domain since the majority of hotspot mutations affects this region. Yet, mutations in other regions such as the proline rich domain may also affect the protein's expression and activity. The aim of this study is to investigate the effect of various positions of mutations in TP53 gene on glycolysis, apoptosis and transcription of p53 target genes. METHODS: Mutations frequency and their effect on p53 expression were assessed by PCR-SSCP, sequencing and immunohistochemistry on 30 ovarian cancer biopsies. Six tumors were cultured, as well as SK-OV-3, OVCAR-3 and Igrov-1. SK-OV-3 cells were transfected with 2 TP53 mutants. p53 transcriptional activity was assayed by qPCR, apoptosis by flow cytometry and glycolysis by glucose and lactate measurements, with quantification of glycolytic enzymes expression. RESULTS: Our results showed a high frequency of the P72R mutant, associated with p53 overexpression in the ovarian biopsies. However, P72R mutant cells showed similar apoptosis and glycolysis as WT cells. DNA binding domain mutations decreased the transcriptional activity of the protein and increased glucose consumption and lactate production. CONCLUSION: Despite the overexpression of the P72R mutated protein in the biopsies, it showed a similar apoptotic activity and glucose regulation ability as WT p53. Knowing that p53 expression status is used for chemotherapeutic approaches and prognosis in ovarian cancer, the results obtained highlight the importance of locating TP53 mutations.

Interplay of long non-coding RNAs and TGF/SMAD signaling in different cancers.

Based on the exciting insights gleaned from decades of ground-breaking research, it has become evident that deregulated signaling pathways play instrumental role in cancer development and progression. Interestingly discovery of non-coding RNAs has revolutionized our understanding related to transcription, post-transcription and translation. Modern era has witnessed landmark discoveries in the field of molecular cancer and non-coding RNA biology has undergone tremendous broadening. There has been an exponential growth in the list of publications related to non-coding RNAs and overwhelmingly increasing classes of non-coding RNAs are adding new layers of complexity to already complicated nature of cancer. Regulation of TGF/SMAD signaling by miRNAs and LncRNAs has opened new horizons for therapeutic targeting of TGF/SMAD pathway. In this review we have set spotlight on central role of LncRNAs in modulation of TGF/SMAD pathway. Major proportion of the available evidence is underlining positive role of LncRNAs in contextual regulation of TGF/SMAD pathway. LncRNAs are vital to these regulatory networks because they provide a background support to make the TGF/SMAD mediated intracellular signaling more smooth or make transduction cascade more flexible in response to cues from extracellular environment. Therefore, in accordance with this notion, MALAT1, OIP5-AS1, MIR100HG, HOTAIR, ANRIL, PVT1, AFAP1-AS1, SPRY4-IT, ZEB2NAT, TUG1 and Lnc-SNHG1 have been reported to positively regulate TGF/SMAD signaling. In this review, we have focused on the regulation of TGF/SMAD signaling by LncRNAs and how these non-coding RNAs can be therapeutically exploited. Short-interfering RNA (siRNA) and natural products are currently being tested for efficacy against different LncRNAs. Nanotechnological strategies to efficiently deliver LncRNA-targeting siRNAs are also currently being investigated in different cancers.

Platelet rich plasma (PRP) induces chondroprotection via increasing autophagy, anti-inflammatory markers, and decreasing apoptosis in human osteoarthritic cartilage.

OBJECTIVES: Autophagy constitutes a defense mechanism to overcome aging and apoptosis in osteoarthritic cartilage. Several cytokines and transcription factors are linked to autophagy and play an important role in the degradative cascade in osteoarthritis (OA). Cell therapy such as platelet rich plasma (PRP) has recently emerged as a promising therapeutic tool for many diseases including OA. However, its mechanism of action on improving cartilage repair remains to be determined. The purpose of this study is to investigate the effect of PRP on osteoarthritic chondrocytes and to elucidate the mechanism by which PRP contributes to cartilage regeneration. METHODS: Osteoarthritic chondrocytes were co-cultured with an increasing concentration of PRP obtained from healthy donors. The effect of PRP on the proliferation of chondrocytes was performed using cell counting and WST8 proliferation assays. Autophagy, apoptosis and intracellular level of IL-4, IL-10, and IL-13 were determined using flow cytometry analyses. Autophagy markers BECLIN and LC3II were also determined using quantitative polymerase chain reaction (qPCR). qPCR and ELISA were used to measure the expression of ADAMDTS-5, MMP3, MMP13, TIMP-1-2-3, aggregan, Collagen type 2, TGF-ß, Cox-2, Il-6, FOXO1, FOXO3, and HIF-1 in tissues and co-cultured media. RESULTS: PRP increased significantly the proliferation of chondrocytes, decreased apoptosis and increased autophagy and its markers along with its regulators FOXO1, FOXO3 and HIF-1 in osteoarthritic chondrocytes. Furthermore, PRP caused a dose-dependent significant decrease in MMP3, MMP13, and ADAMTS-5, IL-6 and COX-2 while increasing TGF-ß, aggregan, and collagen type 2, TIMPs and intracellular IL-4, IL-10, IL-13. CONCLUSION: These results suggest that PRP could be a potential therapeutic tool for the treatment of OA.

MicroRNA Regulation of Telomerase Reverse Transcriptase (TERT): Micro Machines Pull Strings of Papier-Mâché Puppets.

Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase. Telomerase reverse transcriptase (TERT) is a multi-talented and catalytically active component of the telomerase-associated protein machinery. Different proteins of telomerase-associated machinery work in a synchronized and orchestrated manner to ensure proper maintenance of telomeric length of chromosomes. Rapidly emerging scientific findings about regulation of TERT by microRNAs has revolutionized our understanding related to the biology of telomeres and telomerase. In this review, we have comprehensively discussed how different miRNAs regulate TERT in different cancers. Use of miRNA-based therapeutics against TERT in different cancers needs detailed research in preclinical models for effective translation of laboratory findings to clinically effective therapeutics.

Regulation of signal transduction cascades by Pterostilbenes in different cancers: Is it a death knell for oncogenic pathways.

Interdisciplinary research has revolutionized the field of medicine and we have witnessed exponential increase in the high-impact research in past few decades. However, the road to this burgeoning research field is obstacle-ridden because of intratumor heterogeneity, loss of apoptosis and dysregulation of spatio-temporally controlled signaling pathways. Ground-breaking findings obtained through genetic, genomic and proteomic studies have considerably improved our concepts related to the complexity of protein network and excitingly, discovery of miRNAs has added another layer of intricacy to quantitatively regulated gene networks. In this review, we chronicle the milestone achievements and discuss how Pterostilbenes effectively regulated different cellular pathways. We have provided detailed mechanistic insights related to regulation of JAK-STAT signaling, Notch pathway, Wnt mediated intracellular signaling by pterostilbene. Underlying mechanisms about regulation of PI3K/AKT and MAPK pathways by pterostilbene in different cancers.  Regulation of Metastasis-associated protein 1 (MTA1) proteins and Human telomerase reverse transcriptase (hTERT) in cancer cells by pterostilbene. Pterostilbene has also been reported to modulate the expression of various oncogenic and tumor suppressor microRNAs in cancer cells. Better and sharper comprehension of the concepts associated with the modes of action of pterostilbene in different cancers will be useful in identification of cancers which can be efficiently targeted by pterostilbene.

The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage.

INTRODUCTION: Local inflammation plays a role in the pathophysiology of osteoarthritis (OA) and chemokines exert catabolic effects on articular cartilage either through paracrine and/or autocrine mechanisms. We sought to compare the expression levels of the chemokine (C-C motif) ligand 20 (CCL20) and its chemokine receptor 6 (CCR6) in donor and osteoarthritic (OA) cartilage and to investigate the role of CCL20 in the pathogenesis of OA and chondrocyte phenotype. METHODS: Cartilage/chondrocytes from donor and OA knee joints was analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. Effects of CCL20 on cytokines and mediators of cartilage degradation were examined by RT-PCR for mRNA expression levels, enzyme-linked immunosorbent assays, and proteoglycan (GAG) assays. RESULTS: CCL20 and CCR6 proteins were abundantly expressed in OA cartilage sections compared to donor sections as judged by immunohistochemistry. RT-PCR of cartilage extracts confirmed the predominance of CCL20/CCR6 mRNA expression in OA cartilage. CCL20 mRNA expression was low in donor chondrocytes but increased after stimulation with proinflammatory cytokines. mRNA expression levels of IL-6, cyclooxygenase-2, and iNOS were elevated in donor chondrocyte cultures treated with rhCCL20. The release of MMP1/13, PGE2, proteoglycan GAG fragments, and IL-6 from cartilage explant cultures was markedly augmented in the presence of CCL-20. CCL-20 stimulated MMP-13, ADAMTS-5, and col type X mRNA but inhibited col type II mRNA expression in freshly explanted and cultured cartilage specimens. CONCLUSIONS: CCL20/CCR6 may play an important role in the pathogenesis of OA by inducing changes in phenotype and catabolic gene expression in chondrocytes.

Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532.

BACKGROUND: Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In this study, we investigated the effect of GR on telomerase activity and on the efficacy of its inhibition by BIBR 1532. METHODS: Breast cancer MDA-MB 231 and MCF-7 cells were cultured in DMEM (Dulbecco's modified eagle's media) with 0, 1 or 4.5 g/l of glucose. The telomerase activity was measured via quantitative Real-Time PCR, and the two telomerase subunits were semi-quantified by RT-PCR. Proliferation test and mitochondrial metabolism were assessed via tetrazolium salt reduction and cell counts; apoptosis was assessed via caspase-3 quantification and flow cytometry. RESULTS: A decrease in the telomerase activity of more than 75% was associated with a significant reduction in the mRNA expression of its catalytic subunit hTERT (Reverse Transcriptase) and a decrease in the mitochondrial metabolism by more than 80% under restricted glucose conditions. In addition, GR increased the effect of BIBR 1532. Glucose deprivation induces apoptosis via BIBR 1532-mediated telomerase inhibition in triple negative breast cancer cells, as assessed by caspase-3 measurements and Annexin analysis. CONCLUSIONS: Taken together, our results suggest that the effect of BIBR 1532 is potentiated by GR to induce triple negative breast cancer cell death.

Stem Cell Secretions as a Potential Therapeutic Agent for Autism Spectrum Disorder: A Narrative Review.

Autism spectrum disorder (ASD) is a neurodevelopmental illness characterized by impaired social interaction and restricted repetitive behaviors or interests. The rising prevalence of ASD diagnosis has triggered a surge in research into investigating the underlying neuropathological processes and finding new therapeutic approaches. ASD is characterized by neuroinflammation and dysregulation of neuro-immune cross-talk, which suggests that stem cell treatment might be a potential therapeutic approach. The beneficial and restorative effects of stem cells are mainly due to their paracrine activity, in which stem cells generate and release extracellular vesicles such as exosomes and distinct secreted non-vesicle soluble proteins, including, growth factors, chemokines, cytokines, and immunomodulatory molecules referred to as the Secretome. In this paper, we reviewed the existing research exploring the therapeutic potential of stem cell secretome focusing on their role in addressing ASD pathology. Furthermore, we proposed a comprehensive mechanism of action for stem cell secretions, encompassing the broader secretome as well as the specific contribution of exosomes, in alleviating ASD neuropathology. Across the reviewed studies, exosomes and secreted soluble factors of the transplanted stem cell demonstrate a potential efficacy in ameliorating autistic-like behaviors. The proposed mechanism of action involves the modulation of signaling pathways implicated in neuroinflammation, angiogenesis, cellular apoptosis, and immunomodulation.

CD154: an immunoinflammatory mediator in systemic lupus erythematosus and rheumatoid arthritis.

Systemic lupus erythematosus and rheumatoid arthritis are two major chronic inflammatory autoimmune diseases with significant prevalence rates among the population. Although the etiology of these diseases remains unresolved, several evidences support the key role of CD154/CD40 interactions in initiating and/or propagating these diseases. The discovery of new receptors (αIIbß3, α5ß1, and αMß2) for CD154 has expanded our understanding about the precise role of this critical immune mediator in the physiopathology of chronic inflammatory autoimmune diseases in general, and in systemic lupus erythematosus and rheumatoid arthritis in particular. This paper presents an overview of the interaction of CD154 with its various receptors and outlines its role in the pathogenesis of systemic lupus erythematosus and rheumatoid arthritis. Moreover, the potential usefulness of various CD154-interfering agents in the treatment and prevention of these diseases is also discussed.

Use of complementary and alternative therapy among patients with rheumatoid arthritis and osteoarthritis.

AIMS AND OBJECTIVES: We wanted to assess the prevalence of complementary and alternative therapy use among patients suffering from rheumatoid arthritis or osteoarthritis in the Lebanese population and to determine the perceived efficacy and side effects of complementary and alternative therapy in the treatment of these diseases. BACKGROUND: Complementary and alternative therapy has become popular among patients with chronic illnesses because of its widespread use. Rheumatoid arthritis and osteoarthritis are two diseases associated with severe pain, inflammation and limited activity. Although both are quite common in Lebanon, no studies were conducted in our country to portray complementary and alternative therapy use in their treatment. DESIGN: Descriptive cross-sectional study. METHODS: Conducted individualised questionnaire-based interviews among 250 adult patients, ranging between the ages of 20-90 years and diagnosed with either rheumatoid arthritis or osteoarthritis. The questionnaire included demographic information, clinical information, use of conventional therapies and complementary and alternative therapy, and the disease status before and after complementary and alternative therapy use. RESULTS: Fifty-eight (23·2%) patients used complementary and alternative therapy in addition to their conventional medications in the treatment of either rheumatoid arthritis or osteoarthritis. Most herbal medicine users (63·8%) believed that complementary and alternative therapy was beneficial. The disease status measured by the intensity of pain, sleeping pattern and level of activities was significantly improved after using complementary and alternative therapy (p =0·01). Forty-eight (82·75%) patients were using herbals as complementary and alternative therapy, 14 (24·1%) of whom have sought medical care because of potential concomitant drug-complementary and alternative therapy side effects. However, these side effects were not serious and reversible. CONCLUSION AND RECOMMENDATIONS: Although complementary and alternative therapy might have beneficial effects in rheumatoid arthritis and osteoarthritis, patients should be cautious about their use and should necessarily inform their health care providers about the consumption of any products other than their conventional medicines. RELEVANCE TO CLINICAL PRACTICE: It is quite essential for health care professionals to be knowledgeable about the use of complementary and alternative medicine therapies when providing medical care to patients with arthritis.

Use of herbal medications and their perceived effects among adults in the Greater Beirut area.

OBJECTIVES: To measure the magnitude of use of so-called "herbal medications" with or without prescribed drugs and to assess the benefits and adverse effects perceived by herbal users in the Greater Beirut area. METHODS: A sample survey of 480 adults (18-65) in the Greater Beirut (GB) area was conducted over a one-month period in 2009. RESULTS: The estimated weighted prevalence of herbal use in the previous 12 months in GB was 58.9% (56.7-61.2). Most of the 293 users (72.4%) believed that their use had been of no benefit, but 70% thought use was relatively safe. Of users, 53% were concomitantly using conventional drugs for a chronic condition yet only 45% had thought of informing their physician about herbal use. Among the "concomitant users" 60% had suffered some form of adverse effects. CONCLUSIONS: There is a relatively high prevalence of herbal medicine use in Greater Beirut, with an important rate of self-reported adverse effects, especially among those who suffer chronic conditions, and little exchange of information on this between patients and doctors. Data indicate the need to educate patients about realities associated with abusive use, expected benefits and potential drug-herb interaction. Patients on chronic medications should not be left to actually experience adverse effects in order to discover that herbal medicines are not always effective or innocuous.

Mesenchymal Stem Cell Exosomes and Cancer: Controversies and Prospects.

Mesenchymal stem cells (MSCs) have displayed a novel therapeutic strategy for a wide range of diseases and conditions. Their secretome and exosome-based paracrine activity are considered as the main processes harboring their diverse therapeutic properties. Several investigations have examined the effects of MSC-derived exosomes on cancer growth, yet, controversial results have always emerged. Although MSC-derived exosomes are able to rigorously enforce the repression of cancer proliferation and progression, it is shown that MSCs exosomal activity displays numerous protumorigenic effects. This discrepancy over the dual effects of MSCs on cancer growth may be mediated by many factors including experimental design, stem cells origins, culture conditions, in addition to cancer-MSCs cross-talks. Despite the controversial effects of MSCs on carcinogenesis, scientists are able to overcome a number of obstacles by modifying MSCs to deliver antioncogenic miRNAs, anticancer drugs, and oncolytic viruses into tumor sites. This review discusses the controversial effects of MSC-derived exosomes on tumorigenesis, investigates the main causes that underlie this discrepancy, summarizes the pattern of engineered-MSCs, and finally highlights how future studies should advance the research in the field of MSCs-based cancer therapies in order to accelerate the transition from preclinical studies to clinical practice.

Real-time reverse transcription-polymerase chain reaction quantification of tumor necrosis factor alpha messenger in human leukocytes.

BACKGROUND: Tumor necrosis factor (TNF)-alpha plays a significant role in the pathogenesis of several inflammatory conditions. Several studies confirmed high TNF-alpha plasma protein levels in such conditions and highlighted the utility of TNF-alpha as a biomarker for disease progression or response to biological therapy. We aimed to provide a novel molecular technique for the measurement of TNF-alpha. METHODS: Quantitative assay for the measurement of TNF-alpha messenger ribonucleic acid (mRNA) was done using real time reverse transcription polymerase chain reaction (RT-PCR). RESULTS: The test was specific, sensitive, and efficient and possessed a wide scale of linearity. Intrassay and interassay CVs were equivalent to those observed in enzyme-linked immunosorbent assay methods for plasmatic TNF-alpha. Data from 11 healthy adults recruited in an attempt to establish reference values showed an average of 109.4 ng of U937 RNA (range: 67.0 - 173.5). Circulating TNF-alpha protein was not detected by ELISA in any of the 11 subjects. CONCLUSIONS: The test may be useful for clinical studies and in research investigating TNF-alpha gene expression both in physiologic and pathologic situations, although these pilot findings need to be confirmed through larger studies.

Mesenchymal Stromal Cell Secretome: Immunomodulation, Tissue Repair and Effects on Neurodegenerative Conditions.

Mesenchymal stromal cells (MSCs) have emerged as a modern development in therapeutics for a wide variety of diseases. Secreted paracrine factors constitute the principal components harboring the restorative promise of MSCs. Recent studies demonstrate that MSC-derived secretomes are composed of several molecules targeting a variety of biological processes that impact tissue repair, growth and immunomodulation. Indeed, secretomes interact with immune cells, activating regulatory anti-inflammatory phenotypes. In this review, we discuss the action of MSC-derived secretomes in promoting tissue regeneration, opposing the inflammatory response in context-specific cases, and treating neurodegenerative diseases, resulting from chronic neuroinflammation.

Craniofacial and traumatic brain injuries in mixed martial arts.

Objective: Mixed-Martial-Arts (MMA) has witnessed a rapid growth over the recent years. This study aims to explore the patterns and trends of head injuries in MMA.Design: Descriptive epidemiological study.Setting: Ringside physician reports of the Ultimate Fighting Championship (UFC) fights between 2016 and 2019 (inclusive) were screened. Data were extracted from the Nevada State Athletic Commission (NSAC) database. Play-by-play video analysis was also conducted.Participants: UFC fighters involved in fights sanctioned by the NSAC, between 2016 and the end of 2019 (N = 816).Independent variables: Sex, location of head injury, type of head injury, injury mechanism, number of significant head strikes, type of finish, and weight division.Main outcome measures: Head injury rates were calculated. A one-way analysis of variance (ANOVA) was used to explore any statistically significant differences between injury rates of different locations, types, and types of finishes. An independent t-test was used to determine whether any significant differences existed between the two sexes, and a Joinpoint regression analysis was used to determine the statistical significance of the trends of head injury rates across different weight divisions. P-values <0.05 were considered significant (95% CI).Results: A total of 288 head injuries in 408 fights were recorded during our study period. Head injury rate constituted 35 injuries per 100 athletic-exposures (AE) in sanctioned fights. Traumatic brain injuries (TBI) were the most common type of injury, with a rate of 16 per 100AE, significantly greater than that of fractures (p = 0.003). Males had a head injury rate of 37 per 100AE, higher than that of females which was 23 per 100AE. Technical Knockout (TKO)/ Knockout(KO) was the type of finish with the highest rate of head injuries, significantly greater than that of decision or submission (p < 0.001). In general, head injury rates were higher as weight divisions increased.Conclusion: Head injuries are prevalent in MMA. Preventive measures need to be implemented to ensure fighter safety and limit injury risk.

Realizing the Potential of Blueberry as Natural Inhibitor of Metastasis and Powerful Apoptosis Inducer: Tapping the Treasure Trove for Effective Regulation of Cell Signaling Pathways.

Blueberries belong to the genus Vaccinium of the family Ericaceae. Rapidly accumulating experimentally verified data is uncovering the tremendous pharmacological properties of biologically active constituents of blueberries against different diseases. Our rapidly evolving knowledge about the multifaceted nature of cancer has opened new horizons to search for different strategies to target multiple effectors of oncogenic networks to effectively inhibit cancer onset and progression. Excitingly, whole blueberry powder and various bioactive constituents (pterostilbene, malvidin-3-galactoside) of blueberries have been shown to efficiently inhibit metastasis in animal models. These results are encouraging and future studies must focus on the identification of cell signaling pathways effectively modulated by blueberries in different cancers. It seems exciting to note that researchers are focusing on metastasis inhibitory effects of blueberry; however, to reap full benefits, it is necessary to take a step back and critically re-interpret the mechanisms used by active components of blueberry to inhibit or prevent metastasis. JAK/STAT, TGF/SMAD, Notch, SHH/GLI, and Wnt/ ß-Catenin have been shown to be directly involved in the regulation of metastasis. However, because of limited studies, it is difficult to critically assess the true potential of blueberry. Loss of apoptosis, metastasis and deregulation of signaling pathways are branching trajectories of molecular oncology. Accordingly, we have to emphasize on these essential facets to realistically claim blueberry as "Superfood". Different clinical trials have been conducted to gather clinical evidence about the chemopreventive role of blueberry or its bioactive components in cancer patients. But it seems clear that because of the lack of sufficient proof-of-concept studies, we cannot extract significant information about the transition of blueberry into the next phases of clinical trials. Overview of the existing scientific evidence revealed visible knowledge gaps and a better understanding of the targets of blueberry will be helpful in efficient and meaningful translation of laboratory findings to clinically effective therapeutics.

The Prowess of Andrographolide as a Natural Weapon in the War against Cancer.

There has been a paradigm shift in our understanding about the multifaceted nature of cancer, and a wealth of information has revealed that single-target drugs are not good enough to provide satisfactory clinical outcomes and therapeutic effects for complex diseases which involve multiple factors. Therefore, there has been a reignition to search for natural products having premium pharmacological activities aim to efficiently target multiple deregulated cellular signaling pathways. Andrographolide, a diterpene lactone from Andrographis paniculata was brought into to the limelight because of its ability to inhibit cancer cell proliferation and induce apoptosis. Here we reviewed andrographolide on cellular pathways regulation including Wnt/ß-catenin, mTOR, VEGF-mediated intracellular signaling, as well as TRAIL-mediated apoptosis to inhibit cancer development.