Intramuscular injections of human placental extract versus conventional symptomatic approaches in radiation-induced oral mucositis, in patients with head and neck cancers, on definitive chemoradiotherapy - A ray of hope?

BACKGROUND: Despite the availability of a wide range of agents, no single treatment exists for the management of radiation-induced oral mucositis, in patients, with head and neck malignancies, on radical chemoradiation; a debilitating and limiting sequela. Human placental extract is one option that has been proposed. AIMS AND OBJECTIVES: This study aimed at evaluating the therapeutic benefits of human placental extract (Placentrex) in the management of radiation-induced oral mucositis in patients on curative intent treatment for head and neck cancers with concurrent chemoradiation, and to compare the observations with other conventional approaches. MATERIAL AND METHODS: Patients presenting to the Department of Radiation Oncology, of a tertiary cancer care center, with biopsy-proven carcinoma of the oral cavity, oropharynx, and hypopharynx, planned for definitive, curative intent chemoradiation, between January 2020 and June 2021, were recruited for this study. The interventional group received a deep intramuscular injection of 2 ml of Placentrex to the deltoid muscle, once-a-day from the 11th fraction of radiation till completion, on treatment and non-treatment days. The control group received supportive, symptomatic, conventional treatments for mucositis. The response was assessed every week during treatment and at the third and sixth months of follow-up and was compared. RESULTS: The study comprised 26 patients, 15 in the interventional group and 11 in the control group. On completion of treatment, 40% in the interventional arm and 81.82% in the control arm had progressed to grade 2 and 3 mucositis (P < 0.05). Treatment interruption was seen in 13% in the interventional arm and 55% in the control arm (P < 0.001). CONCLUSIONS: Results from this study show that human placental extract, injection Placentrex, had a significant effect in decreasing the severity of radiation-induced mucositis and thereby reducing any interruption or delay in treatment when compared to other conventional methods.

Therapeutic implication of human placental extract to prevent liver cirrhosis in rats with metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH) is always accompanied with hepatic fibrosis that could potentially progress to liver cirrhosis and hepatocellular carcinoma. Employing a rat model, we evaluated the role of human placental extract (HPE) to arrest the progression of hepatic fibrosis to cirrhosis in patients with MASH. SHRSP5/Dmcr rats were fed with a high-fat and high-cholesterol diet for 4 weeks and evaluated for the development of steatosis. The animals were divided into control and treated groups and received either saline or HPE (3.6 ml/kg body weight) subcutaneously thrice a week. A set of animals were killed at the end of 6th, 8th, and 12th weeks from the beginning of the experiment. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatic malondialdehyde (MDA), and glutathione content were measured. Immunohistochemical staining was performed for α-smooth muscle actin (α-SMA), 4-hydroxy-2-nonenal (4-HNE), collagen type I, and type III. Control rats depicted progression of liver fibrosis at 6 weeks, advanced fibrosis and bridging at 8 weeks, and cirrhosis at 12 weeks, which were significantly decreased in HPE-treated animals. Treatment with HPE maintained normal levels of MDA and glutathione in the liver. There was marked decrease in the staining intensity of α-SMA, 4-HNE, and collagen type I and type III in HPE treated rats compared with control animals. The results of the present study indicated that HPE treatment mediates immunotropic, anti-inflammatory, and antioxidant responses and attenuates hepatic fibrosis and early cirrhosis. HPE depicts therapeutic potential to arrest the progression of MASH towards cirrhosis.

Human placental extract regulates polarization of macrophages via IRGM/NLRP3 in allergic rhinitis.

Allergic rhinitis (AR) is globally prevalent and its pathogenesis remains unclear. Alternative activation of macrophages is suggested in AR and thought to be involved in natural immunoregulatory processes in AR. Aberrant activation of Nod-like receptor protein 3 (NLRP3) inflammasome is linked with AR. Human placenta extract (HPE) is widely used in clinics due to its multiple therapeutic potential carried by diverse bioactive molecules in it. We aim to investigate the effect of HPE on AR and the possible underlying mechanism. Ovalbumin (OVA)-induced AR rat model was set up and treated by HPE or cetirizine. General manifestation of AR was evaluated along with the histological and biochemical analysis performed on rat nasal mucosa. A proteomic analysis was performed on AR rat mucosa. Mouse alveolar macrophages (MH-S cells) were cultured under OVA stimulation to investigate the regulation of macrophages polarization. The morphological changes and the expression of NLRP3 inflammasome and immunity-related GTPase M (IRGM) in nasal mucosa as well as in MH-S cells were evaluated respectively. The results of our study showed the general manifestation of AR along with the histological changes in nasal mucosa of AR rats were improved by HPE. HPE suppresses NLRP3 inflammasome and the decline of IRGM in AR rats and MH-S cells. HPE regulates macrophage polarization through IRGM/NLRP3. We demonstrated that HPE had protection for AR and the protection is achieved partly through suppressing M1 while promoting M2, the process which is mediated by IRGM via inhibiting NLRP3 inflammasome in AR.

Placental Extract and Exosomes Derived from Pregnant Mice Attenuate the Development of Experimental Autoimmune Encephalomyelitis.

Placental extract (PE) and exosomes from pregnant mice appear to have immunomodulatory and neuroprotective effects. In this study, we assessed the potential therapeutic effects of PE and exosomes obtained from pregnant mice in experimental autoimmune encephalomyelitis (EAE) mouse models. C57BL/6 mice, 8 to 12 weeks of age, were prepared and administered PE, exosomes, and glatiramer acetate (GA), as an FDA-approved treatment for multiple sclerosis (MS), after EAE induction. Thereafter, the therapeutic effects of treatment were evaluated by measuring the clinical courses of the mice as well as determining the number of regulatory T (Treg) cells using flow cytometry, cytokine levels, and microRNA-326 expression via real-time PCR. GA, PE, and exosomes reduced clinical severity, the extent of spinal cord demyelination, and the infiltration of inflammatory cells into the spinal cord. The frequency of CD4+CD25+FoxP3+ Treg cells increased after treatment of EAE mice with GA, PE, and exosomes. The mRNA expression of the inflammatory cytokines (interleukin-17  and interferon-gamma), as well as miR-326 expression, decreased significantly in the EAE mice after treatment with GA and exosomes. PE and exosomes from pregnant mice are involved in the modulation of Treg/Th17 balance and provide a therapeutic approach for MS. Further clinical studies will hopefully confirm the safety and efficacy of such treatments in MS patients.

Centro de Histoterapia Placentaria "Dr. Carlos Manuel Miyares Cao", 35 años de entrega a la Ciencia Cubana / "Dr. Carlos Miyares Cao" Placental Histotherapy Center, 35 years of dedication to Cuban Science

Introducción: La fundación del Centro de Histoterapia Placentaria, el 25 de abril de 1986, como resultado de la repercusión internacional por el nuevo método cubano del tratamiento del vitiligo con un medicamento obtenido de la placenta humana, descubierto por el doctor Carlos Manuel Miyares Cao, favoreció el desarrollo de las Ciencias Médicas en Cuba. Institución de prestigio, que arribó este 2021 a su Aniversario 35, y que ha obtenido un gran impacto en la salud y calidad de vida de personas con enfermedades dermatológicas como vitiligo, psoriasis y alopecia. Objetivo: Conocedores de la importancia de salvaguardar los hitos históricos como elementos imprescindibles en la trayectoria científico-social de una institución, nos propusimos exponer los componentes fundamentales que conforman este Centro de Histoterapia Placentaria e incentivar a las nuevas generaciones para continuar la labor investigativa que realiza este y la necesidad de preservar su historia. Material y Métodos: Se realizó una investigación histórico-bibliográfica de los documentos compilados que se conservan en la Biblioteca del Centro para poder fundamentar este artículo. Desarrollo: Se incluyen los aspectos esenciales que avalan la historia del Centro y la imbricación científico-social-humana en este del Dr. Carlos Manuel Miyares Cao. Conclusiones: Históricamente ofrecer toda la trayectoria de este Centro de Histoterapia Placentaria y su significación e importancia para la Ciencia Cubana, así como transmitir a especialistas, médicos y, en general, trabajadores de la salud, su destacada labor en la recuperación de graves enfermedades que aquejan a la población mundial(AU)

Introduction: As a result of the international repercussion of a new Cuban method for treating vitiligo with a drug obtained from human placenta, discovered by Dr. Carlos Manuel Miyares Cao, the Placental Histotherapy Center was founded on April 25, 1986 to support the development of Medical Sciences in Cuba. This prestigious institution, which arrived to its 35th Anniversary this year, has made a significant impact on the health and quality of life of people with dermatological diseases such as vitiligo, psoriasis and alopecia. Objective: Knowing the importance of safeguarding historical milestones as essential elements in the scientific and social trajectory of an institution, we intend to present the fundamental components that make up the Placental Histotherapy Center as well as to encourage new generations to continue the research work carried out in this center and the need to preserve its history. Material and Methods: A historical and bibliographical investigation of the documents preserved in the Library of the Center was carried out to base this article. Development: The essential aspects that support the history of the Center as well as the scientific, social and human involvement of Dr. Carlos Manuel Miyares Cao in this process are included. Conclusions: Our objective is to offer the entire trajectory of the Placental Histotherapy Center and its significance and importance for Cuban Science from a historical perspective as well as to inform specialists, doctors, and health workers in general about its outstanding work related to the recovery from serious diseases that afflict the world's population(AU)

Doctor Carlos Manuel Miyares Cao, paradigma de médico / Dr. Carlos Manuel Miyares Cao, an example of an outstanding doctor

José Martí sentenció: "Saberse sacrificar es el precio del éxito durable en todo", y con grandes sacrificios y éxitos en su vida laboral se resume la obra del Dr. Carlos Manuel Miyares Cao, un médico excepcional que supo vincular sus responsabilidades administrativas con la investigación y desarrollo, y la asistencia médica. Incansable luchador por los avances de la Medicina, gestor de la Escuela Cubana de Farmacología, representa un gran ejemplo para los médicos cubanos y de Latinoamérica. Durante su vida estudiantil, colaboró de forma destacada en las actividades que se desarrollaban en la época, siendo fundador de las milicias revolucionarias. Miyares Cao fue uno de los estudiantes de Medicina, fundador integrante de la Milicia Universitaria José Antonio Echeverría, quien con la simbólica camisa rojo vino, pantalón gris y boina negra, desfilaría el 27 de noviembre de 1959 desde la Universidad hasta la explanada de La Punta para rendir tributo a los 8 estudiantes de Medicina, y al decir de él, uno de sus más fraternales compañeros de estudios: ;lo recuerdo muy claro, alto, que por su estatura iba entre las filas finales, con su rifle y marchando con marcada disciplina, tal cual fue en su vida", con sus palabras reflejó los preceptos conceptuales que connotaron su existencia". El Dr. Miyares fue nombrado entre los primeros Instructores no graduados en la cátedra de Farmacología de la Facultad de Medicina de la Universidad de La Habana, tras la renuncia de los profesores universitarios. Asimismo, fundador de la AJR (Asociación Jóvenes Rebeldes) y Unión de Jóvenes Comunistas (UJC universitaria). Tuvo el privilegio de ser de los primeros egresados de la Revolución y su graduación, presidida, en el oriental Pico Turquino, por Fidel Castro, en 1965(AU)

José Martí said: "Knowing how to sacrifice is the price of lasting success for everything". The working life of Dr. Carlos Manuel Miyares Cao is summed up in great sacrifice and success. He was an outstanding doctor who knew how to link his administrative responsibilities to research and development and medical care. As a tireless fighter for the advances of medicine, he was the founder of the Cuban School of Pharmacology and a notable example for Cuban and Latin American doctors. During his student life, he collaborated with important activities that took place at his time, being founder of the revolutionary militias. During his medical studies, he was a founder member of the University Militias "José Antonio Echeverría". Wearing the symbolic red wine shirt, gray pants and black beret, he paraded on November 27, 1959 from the university to the Punta esplanade to pay tribute to the 8 medical students. One of his most fraternal fellow students says, "... I remember him very clearly; he was tall and because of his height he was among the ranks of the final lines; with his rifle he used to march with the discipline that characterized him during all his life." With his words, he illustrated the principles and convictions that marked his existence. After the resignation of university professors, Dr. Miyares was appointed among the first undergraduate Pharmacy instructors at the Department of Pharmacology of the School of Medicine of the University of Havana. He was also the founder of the AJR (Association of Young Rebels) and the UJC (Union of Young Communists) in the university. He had the privilege to be one of the first graduates after de triumph of the Revolution. His graduation, which was held at Pico Turquino in eastern Cuba, was presided by Fidel Castro in 1965(AU)

Horse Placental Extract Enhances Neurogenesis in the Presence of Amyloid ß.

Human placental extract and animal-derived placental extracts from pigs and horses host a wide range of biological activities. Several placental products are used as medicines, cosmetics, and healthcare substances worldwide. However, the use of placental extracts for neuronal functioning is currently not established because the number of relevant studies is limited. A few previous reports suggested the neuroprotective effect and dendrite genesis effect of placental extract. However, no studies have reported on neurogenesis in placental extracts. Therefore, we aimed to investigate the effects of horse placental extract on neurogenesis, and we examined the protective effect of the extract on the onset of memory disorder. A horse placental extract, JBP-F-02, was used in this study. JBP-F-02 treatment dose-dependently increased the number of neural stem cells and dendrite length under Aß treatment in primary cultured cortical cells. The oral administration of JBP-F-02 to a 5XFAD mouse model of Alzheimer's disease at a young age significantly prevented the onset of memory dysfunction. This study suggests that the extract has the potential to prevent dementia.

Efficacy and safety of Hominis placenta pharmacopuncture on mild cognitive impairment: Randomized, double blind, placebo-controlled, multi-center trial.

INTRODUCTION: Mild cognitive impairment (MCI) is cognitive decline which can be observed in a wide range of cognitive domains. It is considered as a prodromal stage of dementia; therefore, strategies for treatment are necessary, but current evidence is limited. Combining the memory enhancing effect of Hominis placenta (H placenta) and acupuncture elucidated separately in previous studies, efficacy of H placenta pharmacopuncture for treating MCI is anticipated. METHODS: Thirty participants will be recruited. Male and female adults aged 50 to 80 who voluntarily participate in the trial, are diagnosed with MCI according to diagnostic and statistical manual of mental disorders-5 criteria, and have a Clinical Dementia Rating score 0.5 will be enrolled. Participants who meet the criteria will be randomly allocated to either pharmacopuncture group or control group. Participants will undergo H placenta pharmacopuncture or saline pharmacopuncture in GV20, ST36, and CV12 twice weekly for 8 weeks and will be evaluated a month after the last treatment. Primary outcome will be difference in mean change of Korean version of Montreal Cognitive Assessment scores between intervention group and control group. Cognition, mood, sleep quality and quality of life will be also assessed using other neuropsychological tests and questionnaires regarding depression, anxiety, sleep and quality of life. DISCUSSION: Evaluating the efficacy and safety data obtained by assessing diverse aspects of patients with MCI will broaden the scope of MCI management and prevention of dementia progression. TRIAL REGISTRATION: Clinical Research Information Service (KCT0005368), Registered 02 Sep 2020, https://cris.nih.go.kr/cris/en/search/search_result_st01.jsp?seq=16425.

Efficacy, safety, and economic assessment of hominis placental pharmacopuncture for chronic temporomandibular disorder: a protocol for a multicentre randomised controlled trial.

BACKGROUND: Temporomandibular disorder (TMD) is a condition encompassing clinical symptoms of the temporomandibular joint, masseter muscle, and surrounding structures. Hominis placental pharmacopuncture (HPP), consisting of human placental extract, has been reported as effective for treating chronic musculoskeletal disorders, but a lack of well-designed randomised controlled trial s (RCTs) mean there is insufficient evidence to prove the efficacy of HPP. METHODS: This study is a two-arm parallel, assessor-blinded, multi-centre, randomised controlled trial. We will enrol 82 chronic TMD patients from rwo Korean Medicine hospitals in Axis 1, Group I according to RDC/TMD diagnostic criteria, and randomly allocate 41 patients each to an HPP group and a physical therapy (PT) group. Treatment will be administered in 10 rounds, after which there will be four follow-up visits 6, 9, 13, and 25 weeks from baseline. The primary end point is 6 weeks after baseline, and the primary outcome is the difference in Visual Analogue Scale (VAS) score for temporomandibular pain between baseline and week 6. Secondary outcomes will be Numeric Rating Scale (NRS) scores for temporomandibular pain and discomfort, temporomandibular joint range of motion, the Korean version of Beck's Depression Index-II (K-BDI-II), Jaw Functional Limitation Scale (JFLS), Patient Global Impression of Change (PGIC) scores, and quality of life. Using data on adverse events and cost-effectiveness in the two groups, we will perform a safety assessment and a cost-effectiveness analysis (economic assessment). DISCUSSION: This study will assess the efficacy and safety of HPP for chronic TMD compared with PT. This RCT will provide evidence for the efficacy, safety, and economics of HPP. TRIAL REGISTRATION: clinicaTrials.gov (NCT04087005) / Clinical Research Information Service (CRIS) (KCT0004437) / IRB (JASENG 2017-09-002-002, KHNMCOH 2019-08-002) / Ministry of Food and Drug Safety (No. 31886).

Therapeutic Benefit of Placentrex in the Management of Acute Chemo Radiation Induced Mucositis in Oral Cancer Patients

Background: A troublesome and usually unavoidable consequence of Head and Neck chemo radiation is oral mucositis which decreases patients' compliance and negatively influences the outcome of therapy by increasing overall treatment time. Currently, no single effective recommended treatment exists for this problem and a variety of supportive care measures have been practiced with limited benefits. This study was done to evaluate the therapeutic benefit of Placentrex in the management of oral mucositis seen in oral cancer patients undergoing treatment with concurrent chemoradiation. Methodology: This study was carried out, as a retrospective analysis, on oral cancer patients undergoing concurrent chemoradiation with weekly Cisplatin regimen treated between Oct 2015 and July 2017. All the patients received 2ml of Inj Placentrex, once daily administered intramuscularly for 4 weeks, NSAIDs, topical analgesics, and mouth wash as treatment for oral mucositis. The results were compared with a historical control group of 40 oral cancer patients who had received treatment prior to the study period without receiving Inj Placentrex as a part of oral mucositis management. Results: Over 60% of the patients in both groups were older than 60 years of age. Buccal mucosa was the predominant sub site of the investigated cancer type. The addition of placentrex resulted in delay in the progression of mucositis, reduction of treatment breaks, regression of pain, and improvement of dysphagia while leading to no adverse effects (p<0.05). Conclusion: Placentrex appears to be a beneficial therapeutic option for the management of concurrent chemo-radiation induced acute oral mucositis in oral cancer patients.

Evaluation of fibroblast growth factor activity exerted by placental extract used as a cosmetic ingredient.

BACKGROUND: The biological activities claimed for placental extract (PE) in its medical and cosmetic applications are largely assumed to be the combined effects of its various signaling molecules and nutritional constituents. But there are considerable uncertainties about this assumption. AIMS: To determine the specific biological activity of PE at a molecular level. METHODS: Fibroblast growth factor (FGF) activity was assessed based on the ability to induce proliferation of FGF receptor (FGFR)-overexpressing BaF3 cells. RESULTS: Porcine PE (PPE), an ingredient in numerous cosmetics, activated proliferation of BaF3 cells overexpressing FGFR subtypes 1c, 2c, 2b, 3c, or 4, that is, all the major FGFR subtypes. The effect was suppressed largely or partially when the cells were treated with a FGFR inhibitor PD173074, and the FGFR-negative BaF3 parent cells exhibited minimal growth promotion as compared to the FGFR-expressing BaF3 cells. The high (>10 kDa) and low (<3 kDa) molecular weight fractions of PPE were effective activators of FGFR signaling. PPE was found to contain sulfated glycosaminoglycans, including heparin/heparan sulfate and chondroitin sulfate, which serve as both structural stabilizers of FGFs and indispensable cofactors for FGF-FGFR signaling. CONCLUSIONS: These results indicate that PPE is capable of evoking FGF signaling in cells via FGFRs. Given that recombinant FGFs have proven useful for medical/cosmetic purposes, our results suggest that the medical/cosmetic utility of PPE is provided at least partly through the activation of FGF signaling in epidermal, dermal, and subdermal tissues.

[Pharmacological treatment of patients with chronic fatigue syndrome]. / Medikamentoznaia terapiia patsientov s sindromom khronicheskoi ustalosti.

AIM: To evaluate the efficacy and safety of human placenta extract - laennec infusions in the treatment of patients with confirmed diagnosis of 'Chronic fatigue syndrome' (CFS). MATERIAL AND METHODS: The study included 38 patients with CFS, randomized into 2 groups: patients of the experimental group (EG, n=24) were treated with 10 intravenous laennec infusions, 4 ml each, 2 times/week, for 5 weeks. The control group (CG) consisted of 14 patients. Treatment efficacy evaluated by the severity of chronic fatigue ('The degree of chronic fatigue' questionnaire), state anxiety, depression and anger (Spilberger test) and quality of life (SF-36v2), exercise tolerance (cardiopulmonary exercise test with gas analysis), blood parameters were assessed before, after, and 5 weeks of follow-up. RESULTS AND CONCLUSION: The EG patients showed a significant reduction in the index of chronic fatigue, which was accompanied by the significant decrease in state depression, anxiety, improvements in subjective assessment of quality of life, as well as a significant increase in physical performance indices (maximal oxygen consumption, anaerobic threshold, load time to failure, normalization of the lipid 'profile' immediately after course of infusions and in 5 weeks follow-up). No changes in chronic fatigue index and other recorded indicators were identified in CG. Laennec did not cause side effects, was well tolerated by all patients.

[Components of human placental extract and its protective effect to rat from D-GalN induced acute liver injury].

Objective: To evaluate the effect of human placental extracts (HPE) on the protection from acute liver injury (ALI) induced by D-GalN and analyze the components of HPE. Methods: (1)Fourty male mice were randomly divided into five groups (Blank, Model, MgIG, HPE and HPE+ MgIG) for the ALI model and treatments.The serum alanine aminotransferase (ALT) and aspartate transaminase (AST) were determined by biochemical assays.Nitric monoxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (T-AOC) in serum and hepatic tissue were detected by assay kits.The extent of liver damage was evaluated by histological examination.(2)Relative molecular mass of HPE was determined by SDS-PAGE.(3) Component identification was performed by using LCMS-TOF.(4)Selected functional molecules in HPE were detected by protein array. Results: (1) A lower level of NO and MDA and a higher SOD and T-AOC were observed in rats treated with HPE compared to the non-treated rats in an acute liver failure disease model.(2) The size of HPE was about 1 200-4 600 by electrophores.(3) 7 peaks of HPE were identified, including uracil, hypoxanthine, tyrosine, phenylalanine, tryptophan, xanthine and thymine.(4) Comparable high concentrations of TGF-ß, IGF-1, IL-9, IL-29 and TNF-α of HPE were revealed by protein array. Conclusions: (1) HPE protects rat from liver damage induced by D-GalN. (2) HPE contains Uracil, hypoxanthine, xanthine, thymine, and functional proteins as TGF-ß, IGF-1, IL-9, IL-29 and TNF-α.

Human Placental Extract as a Subcutaneous Injection Is Effective in Chronic Fatigue Syndrome: A Multi-Center, Double-Blind, Randomized, Placebo-Controlled Study.

Chronic fatigue (CF) is a common reason for consulting a physician due to affecting quality of life, but only a few effective treatments are available. The aim of this study was to examine the effectiveness of subcutaneous injection of the human placental extract (HPE) on medically indescribable cases of CF and safety in a randomized, double-blind, placebo-controlled clinical trial. A total of 78 subjects with CF were randomly assigned to either a HPE group or a placebo group. Subjects in the HPE group were treated with HPE three times a week subcutaneously for 6 weeks, whereas those in the placebo group with normal saline. Then, the fatigue severity scale (FSS), visual analog scale (VAS) and multidimensional fatigue inventory (MFI) were measured in both CF group and chronic fatigue syndrome (CFS) and idiopathic chronic fatigue (ICF) subgroup. The FSS, VAS and MFI score at baseline were not different between the HPE and placebo group in total subjects with CF. In CFS group, the FSS (p=0.0242), VAS (p=0.0009) and MFI (p=0.0159) scores measured at the end of the study period decreased more in the HPE group than in the placebo group when compared with those at the baseline. There were no significant differences between the HPE group and placebo group in the mean change from baseline in FSS, VAS, and MFI in subjects with ICF during the study period. The subcutaneous injection of HPE was effective in the improvement of CFS.

Combined effects of mineral trioxide aggregate and human placental extract on rat pulp tissue and growth, differentiation and angiogenesis in human dental pulp cells.

OBJECTIVE: The aim of this study was to evaluate the combined effects of mineral trioxide aggregate (MTA) and human placental extract (HPE) on cell growth, differentiation and in vitro angiogenesis of human dental pulp cells (HDPCs) and to identify underlying signal transduction mechanisms. In vivo dental pulp responses in rats for a pulp-capping agent were examined. MATERIALS AND METHODS: MTS assay. ALP activity test, alizarin red S staining and RT-PCR for marker genes were carried out to evaluate cell growth and differentiation. HUVEC migration, mRNA expression and capillary tube formation were measured to evaluate angiogenesis. Signal transduction was analysed using Western blotting and confocal microscopy. The pulps of rat maxillary first molars were exposed and capped with either MTA or MTA plus HPE. Histologic observation and scoring were performed. RESULTS: Compared to treatment of HDPCs with either HPE or MTA alone, the combination of HPE and MTA increased cell growth, ALP activity, mineralized nodules and expression of marker mRNAs. Combination HPE and MTA increased migration, capillary tube formation and angiogenic gene expression compared with MTA alone. Activation of Akt, mammalian target of rapamycin (mTOR), p38, JNK and ERK MAPK, Akt, and NF-κB were significantly increased by combining HPE and MTA compared with MTA alone. Pulp capping with MTA plus HPE in rats showed superior dentin bridge formation, odontoblastic layers and dentinal tubules and lower inflammatory cell response, compared to the MTA alone group. CONCLUSIONS: This study demonstrates for the first time that the use of MTA with HPE promotes cell growth, differentiation and angiogenesis in HDPCs, which were associated with mTOR, MAPK and NF-κB pathways. Direct pulp capping with HPE plus MTA showed superior results when compared with MTA alone. Thus, the combination of MTA and HPE may be useful for regenerative endodontics.

Does Topical Application of Placental Extract Gel on Postoperative Fibrotomy Wound Improve Mouth Opening and Wound Healing in Patients With Oral Submucous Fibrosis?

PURPOSE: Placental extract has been used as a therapeutic agent with application in various fields of medicine. Placental extract is well known for its effects on wound healing with anti-inflammatory, antiplatelet, and angiogenic effects and is also a biogenic modulator. The present study evaluated the effect of placental extract on wound healing, mouth opening, and postoperative patient discomfort in patients with oral submucous fibrosis treated with fibrotomy with buccal fat pad coverage and coronoidectomy. MATERIALS AND METHODS: Ten subjects with oral submucous fibrosis who presented with mouth opening less than 20 mm were enrolled in the present prospective randomized controlled trial to assess the effects of placental extract on the fibrotomy wound covered with a pedicled buccal pad fat (5 patients allocated to the study group, group S and 5 to the control group, group C). The following criteria were used to analyze the postoperative effect of placental extract on fibrotomy wounds compared with that of the controls: subjective assessment of the wound, postoperative discomfort, and postoperative mouth opening assessed at 1, 2, and 4 weeks postoperatively. RESULTS: The average difference in the preoperative and fourth week postoperative mouth opening for group C was 13.8 ± 2.68 mm and was 21.20 ± 2.77 mm in group S. The median calculated for group C was a 15.0-mm increase in mouth opening and was 20.0 mm in group S. CONCLUSION: The results obtained with topical application of placental extract on fibrotomy wound healing and postoperative mouth opening were superior to those of the control group in whom placental extract was not used.

Anti-fatigue effects of porcine placenta and its amino acids in a behavioral test on mice.

Placenta extracts are used for their health benefits; however, the anti-fatigue effects of placenta have not been elucidated. Thus, we investigated the anti-fatigue effects of porcine placenta extract (PE) and the amino acids present in the PE (glycine, Gly; proline, Pro; glutamic acid, GA; and arginine, Arg) using a forced swimming test (FST) and a tail-suspension test (TST) on mice. Whole PE or individual amino acids decreased immobility times in the FST. PE, Pro, and Arg all lowered blood levels of lactic acid and alanine aminotransferase (ALT). PE and Gly improved glycogen content and catalase activity. As determined from the serum after the FST: PE regulated the effects of interferon (IFN)-γ and tumor necrosis factor (TNF)-α; GA regulated the effects of IFN-γ; Gly and Arg regulated the effects of interleukin (IL)-6; and all of the amino acids present in PE regulated the effects of TNF-α. As determined from the spleen after the FST: Gly and Arg regulated the effects of IL-1ß; Gly, Pro, and Arg regulated the effects of IL-6; PE and all of the amino acids present in PE regulated the effects of TNF-α. After the TST, PE and all of the amino acids present in PE reduced immobility duration as well as levels of aspartate aminotransferase and ALT. As determined from the serum after the TST: PE and Gly regulated the effects of TNF-α; Gly and Arg regulated the effects of IL-1ß; Gly, Pro, and Arg regulated the effects of IL-6; PE and all of the amino acids present in PE regulated the effects of TNF-α. These results suggest that PE should be considered a candidate anti-fatigue agent.

Complex regional pain syndrome type 1 relieved by acupuncture point injections with placental extract.

This is a case report of a female patient who developed complex regional pain syndrome in the left upper limb after a traumatic injury to the distal part of the left forearm. The pain was immediate and resistant to oral analgesics and continued transcutaneous electrical nerve stimulation. Five months after the injury, the patient presented to our clinic with severe pain, swelling, redness, cold sensation of the left hand, and loss of function from the left hand up to the left shoulder. Acupuncture points LI5, LU2, SI10, HT1, GB21, and SI11 (which are localized in the joints or in the muscles responsible for the movement of the left upper limb) were selected for the application of the placental extract. Injection of placental extract into the acupuncture points resulted in dramatic pain relief, swelling remission, motor recovery, temperature normalization, and disappearance of redness in this patient with complex regional pain syndrome type 1.

Human placental extract reduces allergic inflammation in a murine allergic rhinitis model.

OBJECTIVES/HYPOTHESIS: In this study, we addressed the immunotherapeutic potential of human placental extract (HPE) in a murine allergic rhinitis (AR) model and explored its immunological mechanisms. STUDY DESIGN: In vivo study using an animal model. METHODS: HPE was administered to BALB/c mice before sensitization with allergen (Dermatophagoides farinae [Derf]) (pre-S group) or after allergen challenge (post-C group). The groups were compared with Derf-treated mice that received no HPE (Derf group) and phosphate buffered saline (PBS)-treated mice (control). Allergic symptom scores, eosinophil counts, and serum Derf-specific IgE levels were measured. mRNA expression levels of interferon (IFN)-γ, T-bet, interleukin (IL)-4, GATA-3, and Foxp3 in nasal mucosa were determined by real-time polymerase chain reaction. IFN-γ, T-bet, IL-4, and GATA-3 were confirmed by Western blotting analysis. Spleen CD4(+) CD25(+) Foxp3(+) T cells were detected using flow cytometry. RESULTS: Rubbing motions, serum Derf-specific IgE, GATA-3 mRNA levels, IL-4 mRNA levels, and tissue eosinophil counts were decreased in both pre-S and post-C groups (all P < 0.05). Western blots showed decreased expression of GATA-3 and IL-4 in both pre-S and post-C groups as compared to the Derf group. An increased percentage of CD4(+) CD25(+) Foxp3(+) T cells and an increased level of Foxp3 mRNA were found in pre-S and post-C groups as compared to those in the Derf group (all P < 0.05). CONCLUSION: Both prophylactic and therapeutic treatments with HPE significantly reduced allergic inflammation in nasal mucosa and had the potential to induce regulatory T cells in a murine model of AR.

Efficacy and safety of human placental extract for alcoholic and nonalcoholic steatohepatitis: an open-label, randomized, comparative study.

Human placental extract (HPE) is a traditional medicine that has been used for the symptomatic treatment of liver disease without any verifying clinical evidence. This study aimed to evaluate the efficacy and safety of HPE in patients with alcoholic or nonalcoholic steatohepatitis (ASH or NASH). We designed this clinical trial as a multicenter, open-label, randomized, comparative noninferiority study to improve the reliability of analyses. The enrollment criteria were limited to ASH or NASH patients with serum alanine aminotransferase (ALT) 1.5-fold higher than the normal level. Patients in the control group were treated with a commercially available mixture of liver extract and flavin adenine dinucleotide (LE­FAD). Intention-to-treat (ITT) analysis was applied to 194 patients, and per-protocol (PP) analysis was available for 154 patients. The rate of primary goal achievement of treatment efficacy was arbitrarily defined as 20% or greater improvement in ALT level compared with the pretreatment level and did not differ significantly between the HPE and control groups [62.9% (44/70) vs. 48.8% (41/84); p=0.0772]. ITT and modified ITT analysis showed results similar to those of PP analysis. Adverse drug reactions (ADRs) of minimal to moderate degree occurred in 3.1% of patients. The ADR and treatment compliance rates were similar in both groups. In conclusion, the clinical value of HPE in the treatment of ASH and NASH is equivalent to that of LE­FAD.