Activated carbon cloth versus silver-based dressings in a population with diabetic foot ulcer: a randomised controlled trial.

OBJECTIVE: Activated carbon cloth (ACC), known as Zorflex dressing, has emerged as an innovative approach in managing bacterial infection in diabetic foot ulcer (DFU) treatment. This pilot study was undertaken to determine the efficacy of Zorflex ACC dressing (Chemviron Carbon Cloth Division, UK) compared to standard silver-based dressing on DFUs. METHOD: An open label, comparative, randomised controlled trial enrolling patients who attended the diabetic foot clinic was conducted between August 2022 and August 2023. The primary endpoint was a difference of 20% in wound area reduction with the ACC dressing compared to silver-based dressing within eight weeks. The secondary endpoints were proportion of complete healing, time to healing and adverse events. RESULTS: The cohort comprised 40 patients. The mean wound reduction percentage at 8 weeks for patients in the ACC arm was 85.40±16.00% compared with 65.08±16.36% in the silver-based dressing arm. Complete healing was observed in six of 20 patients in the ACC arm compared to two of 20 in the silver-based dressing arm. CONCLUSION: These data suggest that the ACC dressing promotes better ulcer healing in DFU patients than the silver-based dressing.

Remodeling Osteoarthritic Articular Cartilage under Hypoxic Conditions.

Osteoarthritis (OA) is one of the leading joint diseases induced by abnormalities or inflammation in the synovial membrane and articular cartilage, causing severe pain and disability. Along with the cartilage malfunction, imbalanced oxygen uptake occurs, changing chondrocytes into type I collagen- and type X collagen-producing dedifferentiated cells, contributing to OA progression. However, mounting evidence suggests treating OA by inducing a hypoxic environment in the articular cartilage, targeting the inhibition of several OA-related pathways to bring chondrocytes into a normal state. This review discusses the implications of OA-diseased articular cartilage on chondrocyte phenotypes and turnover and debates the hypoxic mechanism of action. Furthermore, this review highlights the new understanding of OA, provided by tissue engineering and a regenerative medicine experimental design, modeling the disease into diverse 2D and 3D structures and investigating hypoxia and hypoxia-inducing biomolecules and potential cell therapies. This review also reports the mechanism of hypoxic regulation and highlights the importance of activating and stabilizing the hypoxia-inducible factor and related molecules to protect chondrocytes from mitochondrial dysfunction and apoptosis occurring under the influence of OA.

Is There an Interconnection between Epithelial-Mesenchymal Transition (EMT) and Telomere Shortening in Aging?

Epithelial-Mesenchymal Transition (EMT) was first discovered during the transition of cells from the primitive streak during embryogenesis in chicks. It was later discovered that EMT holds greater potential in areas other than the early development of cells and tissues since it also plays a vital role in wound healing and cancer development. EMT can be classified into three types based on physiological functions. EMT type 3, which involves neoplastic development and metastasis, has been the most thoroughly explored. As EMT is often found in cancer stem cells, most research has focused on its association with other factors involving cancer progression, including telomeres. However, as telomeres are also mainly involved in aging, any possible interaction between the two would be worth noting, especially as telomere dysfunction also contributes to cancer and other age-related diseases. Ascertaining the balance between degeneration and cancer development is crucial in cell biology, in which telomeres function as a key regulator between the two extremes. The essential roles that EMT and telomere protection have in aging reveal a potential mutual interaction that has not yet been explored, and which could be used in disease therapy. In this review, the known functions of EMT and telomeres in aging are discussed and their potential interaction in age-related diseases is highlighted.

Pathophysiological Perspective of Osteoarthritis.

Osteoarthritis (OA) is the most well-known degenerative disease among the geriatric and is a main cause of significant disability in daily living. It has a multifactorial etiology and is characterized by pathological changes in the knee joint structure including cartilage erosion, synovial inflammation, and subchondral sclerosis with osteophyte formation. To date, no efficient treatment is capable of altering the pathological progression of OA, and current therapy is broadly divided into pharmacological and nonpharmacological measures prior to surgical intervention. In this review, the significant risk factors and mediators, such as cytokines, proteolytic enzymes, and nitric oxide, that trigger the loss of the normal homeostasis and structural changes in the articular cartilage during the progression of OA are described. As the understanding of the mechanisms underlying OA improves, treatments are being developed that target specific mediators thought to promote the cartilage destruction that results from imbalanced catabolic and anabolic activity in the joint.

Effect of Nigella sativa and its bioactive compound on type 2 epithelial to mesenchymal transition: a systematic review.

BACKGROUND: Nigella sativa or commonly known as black seed or black cumin is one of the most ubiquitous complementary medicine. Epithelial to mesenchymal transition (EMT) of type 2 is defined by the balance between wound healing and tissue fibrosis, which is dependent to the state of inflammation. This systematic review is conducted to provide an overview regarding the reported effect of Nigella sativa and its bioactive compound on the type 2 EMT. METHODS: A search was done in EBSCOHOST, OVID and SCOPUS database to obtain potentially relevant articles that were published between 1823 and August 2019. This review includes studies that focus on the effect of Nigella sativa and its bioactive compound on the events related to type 2 EMT. RESULTS: A total of 1393 research articles were found to be potentially related to the effect of Nigella sativa and its bioactive compound, thymoquinone on Type 2 EMT. After screening was done, 22 research articles met inclusion criteria and were included in this review. Majority of the studies, reported better wound healing rate or significant prevention of tissue inflammation and organ fibrosis following Nigella sativa or thymoquinone treatments. In terms of wound healing, studies included reported progression of EMT related pathological changes after treatment with Nigella sativa or thymoquinone. Alternatively, in terms of fibrosis and inflammation, studies included reported reversal of pathological changes related to EMT after treatment with Nigella sativa or thymoquinone. CONCLUSION: Through this review, Nigella sativa and thymoquinone have been associated with events in Type 2 EMT. They have been shown to promote wound healing, attenuate tissue inflammation, and prevent organ fibrosis via regulation of the EMT process.

COVID-19 and Prostatitis: A Review of Current Evidence.

Coronavirus disease 2019 (COVID-19), a highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), poses a global health threat. The virus enters host cells by binding with angiotensin-converting enzyme 2 (ACE2), which is then facilitated by the protease activity of transmembrane serine protease 2 (TMPRSS2). It triggers a cytokine storm that eventually leads to cell apoptosis, tissue damage, and organ failure. Therefore, any organs in the human body that have both receptors are highly susceptible to COVID-19 infection, potentially resulting in multiple-organ failure. The prostate has been reported to express high levels of ACE2 and TMPRSS2. While there are limited studies regarding the association between COVID-19 and prostatitis, the possibility that SARS-CoV-2 could cause prostatitis cannot be denied. Thus, through this review, a better insight into the associations of SAR-CoV-2 can be provided.

Treatment of prostatitis with low-intensity extracorporeal shockwave therapy (LI-ESWT).

BACKGROUND: Prostatitis is known as the inflammation of the prostate. The treatments of prostatitis are either pharmacological or non-pharmacological treatment. However, some of the treatments are not effective and very invasive which can lead to side effects. Thus, low-intensity extracorporeal shockwave therapy (LI-ESWT) is used as an alternative treatment for prostatitis due to its convenient and non-invasive procedure. However, a definite protocol for this treatment is not available due to the variability of the treatment protocols and the lack of research comparing the efficacy of these protocols. OBJECTIVE: To review and compare the efficacy of different LI-ESWT protocols in treating prostatitis. METHODS: The study was performed by comparing the intensity, duration, frequency and combination with different types of pharmacotherapy drugs of the different LI-ESWT protocols from various studies. The finding from various studies which consist of disease improvement and quality of life (QoL) were also presented in this review. RESULT: From the findings, the protocol can be categorized into three different intensities which are at 3000 pulses, < 3000 pulses and > 3000 pulses. Most studies reported that each protocol is very effective and safe to use and can improve CP symptoms, urinary symptoms, erectile function and QoL. It is also found that no complications or adverse effects occur to the patient. CONCLUSION: Most of the LI-ESWT protocols described are safe and effective in treating CP through the absence of treatment-related adverse effects and maintenance of clinical effects.

Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome patients with erectile dysfunction.

INTRODUCTION: In this study, the efficacy of low intensity shock wave therapy (LSWT) in improving symptoms of chronic pelvic pain syndrome (CPPS) and erectile dysfunction (ED) was investigated. METHODS: Men diagnosed with CPPS and ED (n = 50) were prescribed with LSWT. The LSWT was administered in 10 sessions over the course of 5 weeks at 3,000 pulses with .25 mJ/mm2 energy flow and 5 Hz frequency. Outcome parameters were measured before and after LSWT. RESULTS: Clinical symptoms related to CPPS and ED were measured using four validated questionnaires namely National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI), the International Index of Erectile Function (IIEF), the International Prostate Symptom Score (IPSS), and Sexual Health Inventory for Men (SHIM). The effect of LSWT on each of the three domains of NIH-CPSI, namely Pain, Symptoms, and Quality of Life (QoL) were also analyzed. Uroflowmetry was measured to assess LSWT effect on urine voiding. The mean baseline CPPS symptoms on NIH-CPSI domains of pain, symptoms and QoL were 9.92 ±â€Š5.72 (mean ±â€ŠSD), 5.14 ±â€Š14.5, and 8.02 ±â€Š3.17, respectively. LSWT resulted in significant reduction of CPPS symptoms on all NIH-CPSI domains (Pain = .9 ±â€Š1.37; Symptoms = .74 ±â€Š1.03; QoL = 1.16 ±â€Š1.78). The baseline means of CPPS symptoms on IIEF, IPSS, and SHIM were 45.42 ±â€Š16.24, 24.68 ±â€Š9.28, and 14.28 ±â€Š6.02, respectively. LSWT significant improved CPPS symptoms on IIEF (49.48 ±â€Š28.30) and IPSS (9.04 ±â€Š7.01) but not on SHIM (16.02 ±â€Š9.85). No statistically significant differences were observed with all uroflowmetry parameters. CONCLUSION: The current study demonstrated for the first time the safety and efficacy of LSWT administered in 10 sessions over 5 weeks in improving symptoms of CPPS and ED without causing any significant adverse effect to the patient.

Specificity of estimating femoral anteversion using linea aspera version for total hip arthroplasty: A three-dimensional computed tomography study.

Femoral anteversion is an important parameter that can prevent complication following total hip arthroplasty (THA) caused by improper positioning of the implant. However, assessing femoral anteversion can be challenging in situation with significant defect of the femoral neck. In this study, linea aspera version was nominated as alternative parameter to femoral anteversion. So, the main objective of this study is to determine whether femoral anteversion correlates with linea aspera version. Cross-sectional study. Three-dimensional images of 100 femora were generated and their femoral anteversion and linea aspera version was measured. Correlation between the parameters was calculated. The mean linea aspera version was 7.27°â€…±â€…12.17° (mean ±â€…standard deviation) while the mean femoral anteversion was 11.84°â€…±â€…10.06°. The linea aspera version was inversely correlated with the femoral anteversion with a correlation coefficient of -0.85. Linea aspera should be considered as an additional bony landmark to assess proper implant positioning in THA.

Molecular Action of Hydroxytyrosol in Wound Healing: An In Vitro Evidence-Based Review.

Hydroxytyrosol (HT) is an essential molecule isolated from the phenolic fraction of olive (Olea europaea). HT has been implicated for its health-stimulating effect mainly due to its antioxidative capacity. The current review summarises and discusses the available evidence, related to HT activities in wound healing enhancement. The literature search of related articles published within the year 2010 to 2020 was conducted using Medline via Ebscohost, Scopus, and Google Scholar databases. Studies were limited to in vitro research regarding the role of HT in wound closure, including anti-inflammation, antimicrobial, antioxidative, and its direct effect to the cells involved in wound healing. The literature search revealed 7136 potentially relevant records were obtained from the database search. Through the screening process, 13 relevant in vitro studies investigating the role of HT in wound repair were included. The included studies reported a proangiogenic, antioxidative, antiaging, anti-inflammatory and antimicrobial effect of HT. The current in vitro evidence-based review highlights the cellular and molecular action of HT in influencing positive outcomes toward wound healing. Based on this evidence, HT is a highly recommended bioactive compound to be used as a pharmaceutical product for wound care applications.

Effect of Kelulut Honey on the Cellular Dynamics of TGFß-Induced Epithelial to Mesenchymal Transition in Primary Human Keratinocytes.

Over-induction of epithelial to mesenchymal transition (EMT) by tumor growth factor beta (TGFß) in keratinocytes is a key feature in keloid scar. The present work seeks to investigate the effect of Kelulut honey (KH) on TGFß-induced EMT in human primary keratinocytes. Image analysis of the real time observation of TGFß-induced keratinocytes revealed a faster wound closure and individual migration velocity compared to the untreated control. TGFß-induced keratinocytes also have reduced circularity and display a classic EMT protein expression. Treatment of 0.0015% (v/v) KH reverses these effects. In untreated keratinocytes, KH resulted in slower initial wound closure and individual migration velocity, which sped up later on, resulting in greater wound closure at the final time point. KH treatment also led to greater directional migration compared to the control. KH treatment caused reduced circularity in keratinocytes but displayed a partial EMT protein expression. Taken together, the findings suggest the therapeutic potential of KH in preventing keloid scar by attenuating TGFß-induced EMT.

Nigella sativa and Its Active Compound, Thymoquinone, Accelerate Wound Healing in an In Vivo Animal Model: A Comprehensive Review.

Nigella sativa (NS) has been reported to have a therapeutic effect towards skin wound healing via its anti-inflammatory, tissue growth stimulation, and antioxidative properties. This review examines all the available studies on the association of Nigella sativa (NS) and skin wound healing. The search was performed in Medline via EBSCOhost and Scopus databases to retrieve the related papers released between 1970 and March 2020. The principal inclusion criteria were original article issued in English that stated wound healing criteria of in vivo skin model with topically applied NS. The search discovered 10 related articles that fulfilled the required inclusion criteria. Studies included comprise different types of wounds, namely excisional, burn, and diabetic wounds. Seven studies unravelled positive results associated with NS on skin wound healing. Thymoquinone has anti-inflammatory, antioxidant, and antibacterial properties, which mainly contributed to wound healing process.

Natural 3D-Printed Bioinks for Skin Regeneration and Wound Healing: A Systematic Review.

Three-dimensional bioprinting has rapidly paralleled many biomedical applications and assisted in advancing the printing of complex human organs for a better therapeutic practice. The objective of this systematic review is to highlight evidence from the existing studies and evaluate the effectiveness of using natural-based bioinks in skin regeneration and wound healing. A comprehensive search of all relevant original articles was performed based on prespecified eligibility criteria. The search was carried out using PubMed, Web of Science, Scopus, Medline Ovid, and ScienceDirect. Eighteen articles fulfilled the inclusion and exclusion criteria. The animal studies included a total of 151 animals with wound defects. A variety of natural bioinks and skin living cells were implanted in vitro to give insight into the technique through different assessments and findings. Collagen and gelatin hydrogels were most commonly used as bioinks. The follow-up period ranged between one day and six weeks. The majority of animal studies reported that full wound closure was achieved after 2-4 weeks. The results of both in vitro cell culture and in vivo animal studies showed the positive impact of natural bioinks in promoting wound healing. Future research should be focused more on direct the bioprinting of skin wound treatments on animal models to open doors for human clinical trials.

Fabrication of Bio-Based Gelatin Sponge for Potential Use as A Functional Acellular Skin Substitute.

Gelatin possesses biological properties that resemble native skin and can potentially be fabricated as a skin substitute for full-thickness wound treatment. The native property of gelatin, whereby it is easily melted and degraded at body temperature, could prevent its biofunctionality for various applications. This study aimed to fabricate and characterise buffalo gelatin (Infanca halal certified) crosslinked with chemical type crosslinker (genipin and genipin fortified with EDC) and physicaly crosslink using the dihydrothermal (DHT) method. A porous gelatin sponge (GS) was fabricated by a freeze-drying process followed by a complete crosslinking via chemical-natural and synthetic-or physical intervention using genipin (GNP), 1-ethyl-3-(3-dimethylaminopropyl) (EDC) and dihydrothermal (DHT) methods, respectively. The physicochemical, biomechanical, cellular biocompatibility and cell-biomaterial interaction of GS towards human epidermal keratinocytes (HEK) and dermal fibroblasts (HDF) were evaluated. Results showed that GS had a uniform porous structure with pore size ranging between 60 and 200 µm with high porosity (>78.6 ± 4.1%), high wettability (<72.2 ± 7.0°), high tensile strain (>13.65 ± 1.10%) and 14 h of degradation rate. An increase in the concentration and double-crosslinking approach demonstrated an increment in the crosslinking degree, enzymatic hydrolysis resistance, thermal stability, porosity, wettability and mechanical strength. The GS can be tuned differently from the control by approaching the GS via a different crosslinking strategy. However, a decreasing trend was observed in the pore size, water retention and water absorption ability. Crosslinking with DHT resulted in large pore sizes (85-300 µm) and low water retention (236.9 ± 18.7 g/m2·day) and a comparable swelling ratio with the control (89.6 ± 7.1%). Moreover no changes in the chemical content and amorphous phase identification were observed. The HEK and HDF revealed slight toxicity with double crosslinking. HEK and HDF attachment and proliferation remain similar to each crosslinking approach. Immunogenicity was observed to be higher in the double-crosslinking compared to the single-crosslinking intervention. The fabricated GS demonstrated a dynamic potential to be tailored according to wound types by manipulating the crosslinking intervention.

Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies.

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

Miswak and oral health: An evidence-based review.

Poor oral health has been associated with several chronic and systemic disease. Currently, the most common method of teeth cleaning is the use of a toothbrush together with dentifrices. However, natural chewing stick such as S. persica miswak is still used in many developing countries due to their low cost and availability. The present review aims to summarize the evidences on effectiveness of miswak in promoting oral health. The search was performed using Medline via Ebscohost, Scopus and Google Scholar database to obtain relevant articles published between 2010 to May 2020 using the following set of keywords 1) Miswak OR Salvadora OR persica AND 2) dental OR caries OR plaque OR oral OR orthodontics. Isolated microbial inhibition studies were excluded from the review due to its well-established wealth of literature. Miswak was administered as ten different forms, namely mouthwash, toothpaste, chewing stick, essential oil, aqueous extract, ethanol extract, probiotic spray, dental varnish, dental cement or chewing gum. All studies reported a positive effect of miswak as an anti-plaque, anti-gingivitis, anti-cariogenic, promotion of gingival wound healing, whitening properties, orthodontic chain preservation, and biocompatibility with oral cells. Miswak in its different forms demonstrated positive effect towards oral health maintenance and management.

Cardioprotective Effects of Honey and Its Constituent: An Evidence-Based Review of Laboratory Studies and Clinical Trials.

Cardiovascular disease is a major public health burden worldwide. Myocardial infarction is the most common form of cardiovascular disease resulting from low blood supply to the heart. It can lead to further complications such as cardiac arrhythmia, toxic metabolite accumulation, and permanently infarcted areas. Honey is one of the most prized medicinal remedies used since ancient times. There is evidence that indicates honey can function as a cardioprotective agent in cardiovascular diseases. The present review compiles and discusses the available evidence on the effect of honey on cardiovascular diseases. Three electronic databases, namely, PubMed, Scopus, and MEDLINE via EBSCOhost, were searched between January 1959 and March 2020 to identify reports on the cardioprotective effect of honey. Based on the pre-set eligibility criteria, 25 qualified articles were selected and discussed in this review. Honey investigated in the studies included varieties according to their geological origin. Honey protects the heart via lipid metabolism improvement, antioxidative activity, blood pressure modulation, heartbeat restoration, myocardial infarct area reduction, antiaging properties, and cell apoptosis attenuation. This review establishes honey as a potential candidate to be explored further as a natural and dietary alternative to the management of cardiovascular disease.