Application of Platelet-Rich Plasma as a Stem Cell Treatment - an Attempt to Clarify a Common Public Misconception.

In recent years, there has been a significant increase in the practice of regenerative medicine by health practitioners and direct-to-consumer businesses globally. Among different tools of regenerative medicine, platelet-rich plasma (PRP) and stem cell-based therapies have received considerable attention. The use of PRP, in particular, has gained popularity due to its easy access, simple processing techniques, and regenerative potential. However, it is important to address a common misconception amongst the general public equating to PRP and stem cells due to the demonstrated efficacy of PRP in treating musculoskeletal and dermatological disorders. Notably, PRP promotes regeneration by providing growth factors or other paracrine factors only. Therefore, it cannot replenish or replace the lost cells in conditions where a large number of cells are required to regenerate tissues and/or organs. In such cases, cell-based therapies are the preferred option. Additionally, other tools of regenerative medicine, such as bioprinting, organoids, and mechanobiology also rely on stem cells for their success. Hence, healthcare and commercial entities offering direct-to-customer regenerative therapies should not mislead the public by claiming that the application of PRP is a stem cell-based therapy. Furthermore, it is important for regulatory bodies to strictly monitor these profit-driven entities to prevent them from providing unregulated regenerative treatments and services that claim a broad variety of benefits with little proof of efficacy, safety concerns, and obscure scientific justification.

Three Members of Transmembrane-4-Superfamily, TM4SF1, TM4SF4, and TM4SF5, as Emerging Anticancer Molecular Targets against Cancer Phenotypes and Chemoresistance.

There are six members of the transmembrane 4 superfamily (TM4SF) that have similar topology and sequence homology. Physiologically, they regulate tissue differentiation, signal transduction pathways, cellular activation, proliferation, motility, adhesion, and angiogenesis. Accumulating evidence has demonstrated, among six TM4SF members, the regulatory roles of transmembrane 4 L6 domain family members, particularly TM4SF1, TM4SF4, and TM4SF5, in cancer angiogenesis, progression, and chemoresistance. Hence, targeting derailed TM4SF for cancer therapy has become an emerging research area. As compared to others, this review aimed to present a focused insight and update on the biological roles of TM4SF1, TM4SF4, and TM4SF5 in the progression, metastasis, and chemoresistance of various cancers. Additionally, the mechanistic pathways, diagnostic and prognostic values, and the potential and efficacy of current anti-TM4SF antibody treatment were also deciphered. It also recommended the exploration of other interactive molecules to be implicated in cancer progression and chemoresistance, as well as potential therapeutic agents targeting TM4SF as future perspectives. Generally, these three TM4SF members interact with different integrins and receptors to significantly induce intracellular signaling and regulate the proliferation, migration, and invasion of cancer cells. Intriguingly, gene silencing or anti-TM4SF antibody could reverse their regulatory roles deciphered in different preclinical models. They also have prognostic and diagnostic value as their high expression was detected in clinical tissues and cells of various cancers. Hence, TM4SF1, TM4SF4, and TM4SF5 are promising therapeutic targets for different cancer types preclinically and deserve further investigation.

Chemoprevention by Microencapsulated Lactiplantibacillus Plantarum LAB12 Against Orthotopic Colorectal Cancer Mice is Associated with Apoptosis and Anti-angiogenesis.

The pathogenesis of colorectal cancer (CRC) is associated with gut dysbiosis that is attributed to unhealthy lifestyles and dietary habits. Consumption of microencapsulated probiotics may potentially restore the gut microbiota in favour of prevention against CRC. This study determined the fate of microencapsulated Lactiplantibacillus plantarum (formerly known as Lactobacillus plantarum) LAB12 in the gastrointestinal tract (GIT) and assessed the chemopreventive effect of microencapsulated L. plantarum LAB12 in vivo. The targeted release of L. plantarum LAB12 from Alg-based microcapsules at the stomach, ileum, caecum and colon of Sprague-Dawley rats was examined by confocal microscopy and qPCR. Microcapsules loaded with L. plantarum LAB12 remained intact in the stomach. Free L. plantarum LAB12 were present in abundance (> 7 log CFU) only in the intestines. Subsequently, the chemopreventive properties of microencapsulated L. plantarum LAB12 were validated against NU/NU nude mice bearing orthotopic transplanted CT-26 CRC (12 female mice; 4-6 weeks old; 20-22 g; n = 6/group). Orthotopic mice pre-supplemented with microencapsulated L. plantarum LAB12 (10 log CFU kg-1 BW for 11 weeks) were presented with significantly (p < 0.05) reduced tumour volume (- 98.87%) and weight (- 89.27%) when compared to control. Western blots indicated that the chemopreventive effect could be attributed to apoptosis and anti-angiogenesis mediated, at least in part, through upregulation of tumour suppressor p53 (+ 45.4%) and pro-apoptotic caspase-3 (+ 82.4%), and downregulation of pro-inflammatory COX-2 (- 57.9%), pro-angiogenic VEGF (- 66.8%) and PECAM-1 (-64.1%). Altogether, this study strongly implied the possibility of having L. plantarum LAB12-loaded microcapsules safely incorporated into food and nutraceutical products for prevention against CRC.

Human Exfoliated Deciduous Teeth Stem Cells: Features and Therapeutic Effects on Neurogenerative and Hepatobiliary-pancreatic Diseases.

Stem cells can multiply into more cells with similar types in an undifferentiated form and differentiate into other types of cells. The great success and key essence of stem cell technology is the isolation of high-quality Mesenchymal Stem Cells (MSCs) with high potency, either with multipotent or pluripotent property. In this line, Stem cells from Human Exfoliated Deciduous teeth (SHEDs) are highly proliferative stem cells from dental pulp and have multipoint differentiation capacity. These cells play a pivotal role in regenerative medicine, such as cell repair associated with neurodegenerative, hepatobiliary, and pancreatic diseases. In addition, stem cell therapy has been widely used to regulate immune response and repair of tissue lesions. This overview captured the differential biological characteristics, and the potential role of stem cell technology and paid special attention to human welfare SHEDs in eliminating the above-mentioned diseases. This review provides further insights into stem cell technology by expanding the therapeutic potential of SHEDs in tissue engineering and cell organ repairs.

Role of the CXCR4-SDF1-HMGB1 pathway in the directional migration of cells and regeneration of affected organs.

In recent years, several studies have reported positive outcomes of cell-based therapies despite insufficient engraftment of transplanted cells. These findings have created a huge interest in the regenerative potential of paracrine factors released from transplanted stem or progenitor cells. Interestingly, this notion has also led scientists to question the role of proteins in the secretome produced by cells, tissues or organisms under certain conditions or at a particular time of regenerative therapy. Further studies have revealed that the secretomes derived from different cell types contain paracrine factors that could help to prevent apoptosis and induce proliferation of cells residing within the tissues of affected organs. This could also facilitate the migration of immune, progenitor and stem cells within the body to the site of inflammation. Of these different paracrine factors present within the secretome, researchers have given proper consideration to stromal cell-derived factor-1 (SDF1) that plays a vital role in tissue-specific migration of the cells needed for regeneration. Recently researchers recognized that SDF1 could facilitate site-specific migration of cells by regulating SDF1-CXCR4 and/or HMGB1-SDF1-CXCR4 pathways which is vital for tissue regeneration. Hence in this study, we have attempted to describe the role of different types of cells within the body in facilitating regeneration while emphasizing the HMGB1-SDF1-CXCR4 pathway that orchestrates the migration of cells to the site where regeneration is needed.

Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer.

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.

Color Stability of a New Rice Husk Composite in Comparison with Conventional Composites after Exposure to Commonly Consumed Beverages in Malaysia.

OBJECTIVE: To evaluate the color stability of a new organic rice husk nanocomposite as compared to four conventional composites after exposure to commonly consumed beverages in Malaysia. METHODS: One hundred and twenty-five disk samples were prepared from a new rice husk-based composite and four other conventional methacrylate-based light-cured composites of shade A2. The samples were immersed in four commonly consumed beverages: coco-based drink, kopi, Chinese tea, and teh tarik for four weeks. The color measurements were carried out every week using the reflectance spectrophotometer according to the CIE L ∗ a ∗ b ∗ color system. Color changes of samples (ΔE) in each week were calculated. Statistical analysis was carried out by performing a mixed ANOVA and Tukey's post hoc test in order to analyse the differences in ΔE. RESULTS: The findings revealed a statistically significant difference of ΔE reading (p < 0.05) among all composites immersed in all four beverages after four weeks. Rice husk composites exhibited lesser color stability as compared to Ceram.X One Universal (p < 0.001) and G-aenial Universal Flo (p < 0.001) but showed higher color stability compared to Solare-X (p < 0.001) and Neofil (p < 0.001). Coffee and Chinese tea had the most significant impact on color changes (p < 0.05) observed in all composites over four weeks of study. CONCLUSION: Rice husk composite showed acceptable color stability. It can be considered as an alternative to conventional composites due to its eco-friendly properties.

Microencapsulated Lactobacillus plantarum LAB12 Showed No Sign of Acute or Sub-chronic Toxicity In Vivo.

Lactic acid bacteria (LAB) with probiotic properties are useful options for prophylactic and therapeutic applications against gastrointestinal diseases. The safety of probiotics should, however, be verified before incorporation into food or drinks. The present study had encapsulated Lactobacillus plantarum LAB12 within microcapsules that could withstand extremely high temperature (up to 100 °C) during pelletisation. The microencapsulated LAB12 were then tested for their acute (single dosing) and sub-chronic (a 90-day feeding) toxicity. For acute toxicity study, six male Sprague-Dawley rats were being administered with a single dose of freeze-dried microencapsulated LAB12 at 11 log CFU/kg BW through oral gavage. No clear treatment-related effects were observed after 14 days. For sub-chronic toxicity study, rodents were randomly divided into four groups (6 rats/sex/group) and treated with 0, 8, 9 and 10 log CFU/kg BW of microencapsulated LAB12 in pellet form. No mortality or treatment-related findings were observed in terms of clinical body weight, water intake, or food consumption. No treatment-related adverse effects were observed in blood and tissue samples. The no-observed-adverse-effect-level (NOAEL) for microencapsulated LAB12 was 2.5 × 1010 CFU/kg BW for both genders. These results imply that LAB12 are likely non-pathogenic and non-toxic.

Cellulose Derivatives Enhanced Stability of Alginate-Based Beads Loaded with Lactobacillus plantarum LAB12 against Low pH, High Temperature and Prolonged Storage.

The susceptibility of probiotics to low pH and high temperature has limited their use as nutraceuticals. In this study, enhanced protection of probiotics via microencapsulation was achieved. Lactobacillus plantarum LAB12 were immobilised within polymeric matrix comprised of alginate (Alg) with supplementation of cellulose derivatives (methylcellulose (MC), sodium carboxymethyl cellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC)). L. plantarum LAB12 encapsulated in Alg-HPMC(1.0) and Alg-MC(1.0) elicited improved survivability (91%) in simulated gastric conditions and facilitated maximal release (∼100%) in simulated intestinal condition. Alg-HPMC(1.0) and Alg-MC(1.0) significantly reduced (P < 0.05) the viability loss of LAB12 (viability loss <7%) when compared to Alg alone (viability loss <13%) under extreme temperatures (75 and 90 °C). Four-week storage of encapsulated LAB12 at 4 °C yielded viable counts >7 log CFU g-1. Alg-MC and Alg-HPMC improved the survival of LAB12 against simulated gastric condition (9.24 and 9.55 log CFU g-1, respectively), temperature up to 90 °C (9.54 and 9.86 log CFU g-1, respectively) and 4-week of storage at 4 °C (8.61 and 9.23 log CFU g-1, respectively) with sustained release of probiotic in intestinal condition (>9 log CFU g-1). These findings strongly suggest the potential of cellulose derivatives supplemented Alg bead as protective micro-transport for probiotic strains. They can be safely incorporated into new functional food or nutraceutical products.

Chitosan coated alginate-xanthan gum bead enhanced pH and thermotolerance of Lactobacillus plantarum LAB12.

The vulnerability of probiotics at low pH and high temperature has limited their optimal use as nutraceuticals. This study addressed these issues by adopting a physicochemical driven approach of incorporating Lactobacillus plantarum LAB12 into chitosan (Ch) coated alginate-xanthan gum (Alg-XG) beads. Characterisation of Alg-XG-Ch, which elicited little effect on bead size and polydispersity, demonstrated good miscibility with improved bead surface smoothness and L. plantarum LAB12 entrapment when compared to Alg, Alg-Ch and Alg-XG. Sequential incubation of Alg-XG-Ch in simulated gastric juice and intestinal fluid yielded high survival rate of L. plantarum LAB12 (95%) at pH 1.8 which in turn facilitated sufficient release of probiotics (>7 log CFU/g) at pH 6.8 in both time- and pH-dependent manner. Whilst minimising viability loss at 75 and 90 °C, Alg-XG-Ch improved storage durability of L. plantarum LAB12 at 4 °C. The present results implied the possible use of L. plantarum LAB12 incorporated in Alg-XG-Ch as new functional food ingredient with health claims.