Technological Interventions Enhancing Curcumin Bioavailability in Wound-Healing Therapeutics.

Wound healing has been a challenge in the medical field. Tremendous research has been carried out to expedite wound healing by fabricating various formulations, some of which are now commercially available. However, owing to their natural source, people have been attracted to advanced formulations with herbal components. Among various herbs, curcumin has been the center of attraction from ancient times for its healing properties due to its multiple therapeutic effects, including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, neuroprotective, and radioprotective properties. However, curcumin has a low water solubility and rapidly degrades into inactive metabolites, which limits its therapeutic efficacy. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, and keep its bioavailability and effectiveness. Different formulations with curcumin have been synthesized, and exist in the form of various synthetic and natural materials, including nanoparticles, hydrogels, scaffolds, films, fibers, and nanoemulgels, improving its bioavailability dramatically. This review discusses the advances in different types of curcumin-based formulations used in wound healing in recent times, concentrating on its mechanisms of action and discussing the updates on its application at several stages of the wound healing process. Impact statement Curcumin is a herbal compound extracted from turmeric root and has been used since time immemorial for its health benefits including wound healing. In clinical formulations, curcumin shows low bioavailability, which mainly stems from the way it is delivered in the body. Henceforth, a carrier system is needed to carry curcumin, guard it against degradation, while maintaining its bioavailability and therapeutic efficacy. This review offers an overview of the advanced technological interventions through tissue engineering approaches to efficiently utilize curcumin in different types of wound healing applications.

Curcumin effects on Leydig cell functions and potential therapeutic uses.

Curcumin has been ascribed with countless therapeutic effects, but its impact on testicular function has been scarcely researched. Leydig cells comprise the androgen-secreting population of the testis and may give rise to Leydig cell tumours (LCTs). Due to their steroid-secreting nature, LCTs entail endocrine, reproductive, and psychological disorders. Approximately 10% are malignant and do not respond to chemotherapy and radiotherapy. The aim of this study was to assess curcumin's impact on Leydig cells' functions and its potential effect on LCT growth. In vitro assays on MA-10 Leydig cells showed that curcumin (20-80 µmol/L) stimulates acute steroidogenesis, both in the presence and absence of db-cAMP. This effect is accompanied by an increase in StAR expression. Regarding curcumin's in vitro cytostatic capacity, we show that 40-80 µmol/L curcumin reduces MA-10 Leydig cells' proliferative capacity, which could be explained by the arrest in G2/M and the reduced viability due to the activation of the apoptotic pathway. Finally, CB6F1 mice were inoculated with MA-10 cells to generate ectopic LCT in both flanks. They received i.p. injections of 20 mg/kg curcumin or vehicle every other day for 15 days. We unveiled curcumin's capacity to inhibit LCT growth as evidenced by reduced tumour volume, weight, and area under the growth curves. No detrimental effects on general health parameters or testicular integrity were observed. These results provide novel evidence of curcumin's effects on the endocrine cell population of the testis and propose this natural compound as a therapeutic agent for LCT.

Treatment on Nature's lap: Use of herbal products in the management of hyperglycemia.

Diabetes mellitus (DM) is characterized by persistently elevated blood glucose concentration that lead to multisystem complications. There are about 400 medicinal plants cited to have a beneficial effect on DM. We must choose products wisely based on data derived from scientific studies. However, a major obstacle in the amalgamation of herbal medicine in modern medical practices is the lack of clinical data on its safety, efficacy and drug interaction. Trials of these herbal products often underreport the side effects and other crucial intervention steps deviating from the standards set by Consolidated Standards of Reporting Trials. Due to a lack of knowledge of the active compounds present in most herbal medicines, product standardization is difficult. Cost-effectiveness is another issue that needs to be kept in mind. In this mini-review, we focus on the anti-hyperglycemic effect of herbal products that are commonly used, along with the concerns stated above.

Receptor tyrosine kinase-like orphan receptor 1 inhibitor strictinin exhibits anti-cancer properties against highly aggressive androgen-independent prostate cancer.

Aim: It is important to identify anti-cancer compounds that can inhibit specific molecular targets to eradicate androgen-receptor negative (ARneg), androgen-independent (AI) prostate cancer, which is an aggressive form of prostate cancer with limited treatment options. The goal of this study was to selectively target prostate cancer cells that have high levels of oncogenic protein Receptor tyrosine kinase-like orphan receptor 1 (ROR1) by using strictinin, a small molecule ROR1 inhibitor. Methods: The methods performed in this study include western blots, methyl thiazolyl tetrazolium (MTT) proliferation assays, phosphatidylserine apoptosis assays, apoptosis flow cytometry (Annexin V, caspase 3/7), migration scratch assays, Boyden chamber invasion assays, and cell cycle flow cytometry. Results: Strictinin was most lethal against PC3 [half-maximal drug inhibitory concentration (IC50) of 277.2 µmol/L], an ARneg-AI cell type that expresses the highest levels of ROR1. Strictinin inhibited ROR1 expression, downstream phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT)-glycogen synthase kinase 3beta (GSK3ß) pro-survival signaling, and epithelial-to-mesenchymal transition markers in PC3 cells. Additionally, strictinin decreased PC3 cell migration and invasion, while increasing S-phase cell cycle arrest. In ARneg-AI DU145 cells, strictinin inhibited ROR1 expression and modulated downstream AKT-GSK3ß signaling. Furthermore, strictinin exhibited anti-migratory, anti-invasive, but minimal pro-apoptotic effects in DU145 cells likely due to DU145 having less ROR1 expression in comparison to PC3 cells. Throughout the study, strictinin minimally impacted the phenotype of normal prostatic epithelial cells RWPE-1 (IC50 of 658.5 µmol/L). Strictinin was further identified as synergistic with docetaxel [combination index (CI) = 0.311] and the combination therapy was found to reduce the IC50 of strictinin to 38.71 µmol/L in PC3 cells. Conclusions: ROR1 is an emerging molecular target that can be utilized for treating prostate cancer. The data from this study establishes strictinin as a potential therapeutic agent that targets ARneg-AI prostate cancer with elevated ROR1 expression to reduce the migration, invasion, cell cycle progression, and survival of prostate cancer.

Mechanism of the Huangguoshu waterfall forest environment's promotive effect on human health in Guizhou, China.

Background: The aim of this study was to investigate the specific mechanisms underlying the human health-promoting effects of the forest environment at Huangguoshu Falls, Guizhou, China. Methods: Ninety-five participants were recruited and an eye tracker was used to record fixation and sweep indices. A questionnaire was also used to evaluate the effects of different subject environments on human emotions, perceived recovery and preferences. Thereafter, 24 participants with chronic fatigue syndrome (CFS) were recruited and the participants' fatigue and stress-related scale indices and inflammatory factor levels were examined. Serum metabolites of the participants under different time waterfall forest interventions were detected by ultra performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS). Results: Eye tracking paradigm analysis showed that the "waterfall" element was the most interesting element for participants and that the "charm" of the waterfall forest environment could be well perceived by participants. Scores on the Fatigue Scale, Anxiety Scale and Depression Scale decreased as the duration of treatment in the waterfall forest environment increased. Levels of inflammatory factors decreased after treatment in the waterfall forest environment. At the same time the level of antioxidants, represented by L-ascorbic acid, increased significantly. Conclusions: The charm of the Huangguoshu waterfall scenery could be perceived by the participants and have a positive modulating effect on mood and cognitive function. In addition, the unique mixture of negative oxygen ions in this environment can increase the content of endogenous antioxidants and balance the metabolism of choline and amino acids.

Essential Oils as a Good Weapon against Drug-Resistant Candida auris.

Candida auris is a recently found Candida species, mainly associated with nosocomial outbreaks in intensive care hospital settings, and unlike other Candida species, it can be transmitted through person-to-person or by contact with surfaces. C. auris is described as resistant to first-line antifungals and, consequently, associated with high mortality. Nowadays, essential oils (EOs) are known to be effective against fungal and bacterial infections. This work aimed to evaluate the effect of four EOs (tea tree, niaouli, white thyme and cajeput) against C. auris. The EO's effect on C. auris planktonic growth was evaluated by the minimum inhibitory concentration determination and by the agar disc diffusion method. Then, the same effect was evaluated on biofilm by colony-forming units' enumeration. The results showed that EOs were able to inhibit the C. auris planktonic growth, with an MIC50 between 0.78 and 1.56% and halos of 20-21 mm for white thyme and tea tree and 13-14 mm for cajeput and niaouli. In addition, the EOs were also able to completely inhibit biofilm formation. Moreover, white thyme and cajeput completely eradicate pre-formed biofilms, while tea tree and niaouli significantly reduce it. Thus, this work demonstrates that EOs are a possible therapeutic alternative and a future perspective for the hard fight against C. auris.

Plants as source of new therapies for endometriosis: a review of preclinical and clinical studies.

BACKGROUND: Given the disadvantages and limitations of current endometriosis therapy, there is a progressive increase in studies focusing on plant-derived agents as a natural treatment option with the intention of achieving high efficiency, avoiding adverse effects and preserving the chance for successful pregnancy. The heterogeneity of these studies in terms of evaluated agents, applied approaches and outcomes illustrates the need for an up-to-date summary and critical view on this rapidly growing field in endometriosis research. OBJECTIVE AND RATIONALE: This review provides a comprehensive overview of plant-derived agents and natural treatment strategies that are under preclinical or clinical investigation and critically evaluates their potential for future endometriosis therapy. SEARCH METHODS: An English language PubMed literature search was performed using variations of the terms 'endometriosis', 'natural therapy', 'herb/herbal', 'plant', 'flavonoid', 'polyphenol', 'phytochemical', 'bioactive', 'Kampo' and 'Chinese medicine'. It included both animal and human studies. Moreover, the Clinicaltrials.gov database was searched with the term 'endometriosis' for clinical trials on plant-derived agents. No restriction was set for the publication date. OUTCOMES: Natural therapies can be assigned to three categories: (i) herbal extracts, (ii) specific plant-derived bioactive compounds and (iii) Chinese herbal medicine (CHM). Agents of the first category have been shown to exert anti-proliferative, anti-inflammatory, anti-angiogenic and anti-oxidant effects on endometrial cells and endometriotic lesions. However, the existing evidence supporting their use in endometriosis therapy is quite limited. The most studied specific plant-derived bioactive compounds are resveratrol, epigallocatechin-3-gallate, curcumin, puerarin, ginsenosides, xanthohumol, 4-hydroxybenzyl alcohol, quercetin, apigenin, carnosic acid, rosmarinic acid, wogonin, baicalein, parthenolide, andrographolide and cannabinoids, with solid evidence about their inhibitory activity in experimental endometriosis models. Their mechanisms of action include pleiotropic effects on known signalling effectors: oestrogen receptor-α, cyclooxygenase-2, interleukin-1 and -6, tumour necrosis factor-α, intercellular adhesion molecule-1, vascular endothelial growth factor, nuclear factor-kappa B, matrix metalloproteinases as well as reactive oxygen species (ROS) and apoptosis-related proteins. Numerous studies suggest that treatment with CHM is a good choice for endometriosis management. Even under clinical conditions, this approach has already been shown to decrease the size of endometriotic lesions, alleviate chronic pelvic pain and reduce postoperative recurrence rates. WIDER IMPLICATIONS: The necessity to manage endometriosis as a chronic disease highlights the importance of identifying novel and affordable long-term safety therapeutics. For this purpose, natural plant-derived agents represent promising candidates. Many of these agents exhibit a pleiotropic action profile, which simultaneously inhibits fundamental processes in the pathogenesis of endometriosis, such as proliferation, inflammation, ROS formation and angiogenesis. Hence, their inclusion into multimodal treatment concepts may essentially contribute to increase the therapeutic efficiency and reduce the side effects of future endometriosis therapy.

Research Progress of Pathogenic Mechanism and Treatment of Helicobacter pylori / 胃肠病学

Helicobacter pylori (Hp) infection is closely related to the occurrence and development of chronic gastritis, peptic ulcer, and gastric cancer. At present, the treatment of Hp is mainly the bismuth-containing quadruple therapy as the first-line treatment to eradicate Hp infection. However, the eradication treatment still faces the challenges related to the rising antibiotic resistance, the decrease in eradication rate year by year, the adverse events, the poor patient's compliance and the dysregulation of gastrointestinal microbiome. Therefore, more and more researches are focusing on finding an effective treatment with the use of natural therapy. This article reviewed the research progress of pathogenic mechanism and treatment of Hp infection.

Physiological and Psychological Effects of Watching Videos of Different Durations Showing Urban Bamboo Forests with Varied Structures.

This study illustrated the physiological and psychological effects of watching videos of different durations showing bamboo forests with varied structures. Physiological indicators, including EEG (electroencephalogram), blood pressure, skin conductance, and pulse, were monitored in 180 Chinese university students (mean age: 20.72 ± 2.56 years) while they were watching bamboo videos. Before and after watching the videos, their psychological indicators, including positive and negative moods, were measured using the Profile of Mood States questionnaire. After watching the bamboo videos of different durations, all of the physiological indicators responded to the stimulation after only 1 min. The indicators showed different trends at 1, 3 and 5 min. EEG decreased and then was maintained at a stable level after 1 min, and the high ß, low ß, and α waves had no significant differences between 1, 3 and 5 min. Blood pressure dropped to a stable state after 3 min, and the decline was significantly different greater after 3 min than after 1 min. Skin conductance increased for 1 to 5 min, and it did not stabilize after a long time (5 min). Pulse decreased after 1 min but increased after 5 min. After watching the videos with bamboo of varying structures, the physiological and psychological indicators showed significantly different changes. Skin conductance significantly increased (mean value: 6.78%), and the amount of sweat was more effectively reduced, thereby reducing tension, when the students viewed videos of sympodial bamboo forests compared with monopodial bamboo forests. Bamboo forests with a higher canopy density (0.83-0.85) could significantly decrease α waves (mean value: 1.50 Hz), relaxing the human body. High ß and low ß waves showed greater decreases, with tension reduced more effectively, when bamboo forests with a low tilt ratio (< 1.5%) were viewed. Bamboo forests with neat undergrowth could have more beneficial physiological and psychological effects on the human body.

Naturopathy in Australia: Where are we now? Where are we heading?

Naturopathy is the general practice of natural therapies. It emphasizes prevention, treatment, and promotion of optimal health through therapeutic modalities which encourage the self-healing process of the body. Formalized in the 19th century by the hydrotherapy and nature cure movement in Austria and Germany, naturopathy was introduced to Australia at the turn of the 20th century. It became popular since the 1970s due to social and cultural change characterized by the post-modern philosophy, as well as government policies highlighting individual responsibility and freedom of choice. Naturopathy is one of the most popular forms of complementary medicine in Australia today with naturopaths received 4.9 million consultations annually. Naturopathic consultations are sought for a variety of conditions and, in some areas, as a form of primary care, especially by middle-aged women who have a higher education level and a higher annual income. The number of Australian naturopaths was estimated to be over 4000 in 2017 and expects to grow to over 4600 by 2022, although this number is likely to be an underestimation. Australian naturopaths, as a predominantly female profession, work mainly in private clinical practice with nutritional medicine, herbal medicine, homeopathy, as well as massage therapies being the most common modalities used. There are also signs of greater integration with community pharmacies and integrative medicine clinics in major cities. The Bachelor's degree programs in Naturopathy has just become the only accredited entry-level qualification since late 2015. Currently, there are only 5 private colleges offering naturopathic education, a far cry from the 40 over in mid-2000. The profession continues to be self-regulated. There is no barrier of entry to practice and unqualified practitioners of naturopathy can potentially do harm to the public. The registration of naturopaths remains unresolved due to fragmented representation under many professional associations, disunity among the profession, and objections by certain health care lobbyists. There is a dearth of research demonstrating efficacy of the whole practice of naturopathy in Australia, which has directed the government's decision to withdraw it from private health insurance coverage from 2019. Moving forward, the whole system research of naturopathy in Australia will be in focus with the recent establishment of a practice-based research network and an international research consortium. With increasing scrutiny from evidence-based medicine, the present and future challenge to Australian naturopaths is centered on the integration of both scientific and traditional evidence to form the foundation of a person-centered, evidence-informed practice.

Apitherapy as a New Approach in Treatment of Palmoplantar Psoriasis.

BACKGROUND: Apitherapy is the medical use of honey bee products, "honey, propolis, royal jelly, bee wax, and bee venom to relieve human ailments. Propolis is one of the most well-documented products derived from the honeybee and has always played an important role in traditional folk medicine. AIM: The aim was to justify the consideration of Aloe Vera as an effective remedy for the treatment of psoriasis. METHODS: The study follows (857) patients (354 females, 503 males) with a mean age range from (9 - 62) years, affected with moderate to severe psoriasis in palms and foot soles treated by a combination mixture of propolis and Aloe in the form of an ointment (Aloreed) and Beauty reed cream. The treatment duration was for 12 weeks. Results were evaluated by using clinical, histological and statistical parameters. RESULTS: After the 12 - week treatment, we observed an 86% overall response rate from which 62% showed excellent results and 24% showed good results, therefore proving the efficiency in the use of the mixture of propolis 50% and aloe vera 3% as topically applied ointment in the treatment of mild to moderate psoriasis. CONCLUSION: Patients who have palmoplantar psoriasis, who were treated with a topically applied mixture of propolis (50%) and aloe vera (3%), have shown noteworthy improvement thus proving the efficiency of propolis and aloe vera in the treatment of mild to moderate psoriasis.

Is There a Place for Local Natural Treatment of Psoriasis?

BACKGROUND: Apitherapy is the medical use of honey bee products (honey, propolis, royal jelly, bee wax, and bee venom) to relieve human ailments, propolis in particularly, rich in essential oils such as flavonoid. Propolis is derived from tree buds and plants. It is considered as one of the most well-documented products from the honeybee and has always played an important role in traditional folk medicine. Another renowned plant is Aloe vera appertaining to the Liliaceae family. Its mucilaginous gel has been extensively used in many cultures for its apparent effectiveness in treating wounds, burns, itchiness and hair loss. AIM: The aim was to assess the efficacy of a mixture in an ointment form of propolis (50%) and aloe vera (3%), in the treatment of mild to moderate psoriasis. METHODS: In this double-blind control study, 2248 patients with both mild to moderate cases of psoriasis were evaluated from 2012 to 2015. RESULTS: In Group 1 the overall response at the end of 12 weeks was as follows: Cleared in 64.4% (excellent response), good response in 22.2%, and weak response in 5.6% and no response in 7.7%. In Group 2 (placebo group) no significant improvement was observed after 12 weeks of treatment. Also, histology also demonstrated a marked reduction in hyperkeratosis and acanthosis. CONCLUSION: In comparison with Group 2 (placebo group) patients in Group 1, treated with a mixture of propolis (50%) and aloe vera (3%), in the form of an ointment have shown noteworthy improvement thus substantiating the therapeutic value of propolis and aloe vera in the treatment of mild to moderate psoriasis.

Prótesis inmediata con analgesia acupuntural en una adulta mayor / Immediate prosthesis with acupunctural analgesia in an elderly

Se describe el caso clínico de una paciente de 62 años de edad, quien temía a los anestésicos dentales convencionales, pero tenía gran preocupación por rehabilitar su estética con prótesis inmediata. Se decidió aplicar anestesia acupuntural y realizar las extracciones dentales para que recibiera el tratamiento deseado. No se manifestaron reacciones adversas y la paciente quedó satisfecha por los resultados obtenidos, así como por las ventajas que ofrece esta terapia natural.

The case report of a 62 years patient is described who was afraid of the conventional dental anesthetics, but she had great concern to rehabilitate her aesthetics with immediate prosthesis. It was decided to apply acupunctural anesthetic and to carry out the dental extractions so that she received the desired treatment. There were not adverse effects and the patient was satisfied with the results obtained, as well as with the advantages of this natural therapy.

Deficiency of G-protein coupled receptor 40, a lipid-activated receptor, heightens in vitro- and in vivo-induced murine osteoarthritis.

Osteoarthritis (OA) is an age-related degenerative joint disease. To date, its management is focused on symptoms (pain and inflammation). Studies suggest that fatty acids can reduce the expression of inflammatory and catalytic mediators, and improve in vivo joint function. Free fatty acid receptors (FFARs) such as G-protein coupled receptor 40 (GPR40) are proposed as attractive therapeutic targets to counteract inflammation and cartilage degradation observed in OA. This study aims to elucidate the involvement of GPR40 in OA. In this study, we used an in vitro model of OA, and surgically induced OA by ligament transection and partial meniscectomy in wild-type and GPR40 deficient mice. OA phenotype was investigated in vivo by histology and genes expression. We demonstrate that IL-1ß-treated GPR40(-/-) chondrocytes secret more inflammatory mediators (nitric oxide, interleukin-6, prostaglandin E2) and active catabolic enzymes (metalloproteinase-2, -9 [MMP-2, MMP-9]), and show decreased anabolism (glycoaminoglycan) compared to GPR40(+/+) cells. In accordance with these results, we show that GPR40(-/-) mice exhibit an aggravated OA-induced phenotype characterized by higher tidemark exposure, frequency of osteophyte formation and subchondral bone sclerosis. Altogether our results demonstrate that GPR40 deficiency leads to an extended OA phenotype, providing evidence that increasing GPR40 activity, by natural or synthetic ligands, could be a new strategy in the management of OA.