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.

Supplementation of equine placenta extract on corneal wound in two dogs: Case report.

Background: Canine corneal disease is a common condition encountered in daily practice. If the depth of corneal damage is limited to the epithelial layer, healing is often straightforward; however, if it extends into the epithelial basement membrane or corneal parenchyma, surgical treatment is the treatment of choice. Moreover, in cases where there is an underlying disease or where the owner refuses surgical treatment, treatment options are often limited to eye drop treatment, which may be inadequate. Case Description: Dogs aged 10 and 14 years were admitted to the hospital with eye injuries. Based on the examination findings, the owner believed that surgical treatment would be effective; however, this could not be performed owing to the underlying condition of the cases. Hyaluronic acid and antibiotic eye drops were administered, but there was no improvement in the eye damage. The eye-drop treatment was prolonged without any improvement, and in the meantime the patients' weakness became apparent. In parallel with the eye-drop treatment, the patients were given a supplement containing equine placental extract to help restore their physical fitness. Consequently, in addition to the recovery of physical fitness, a film gradually formed over the eye damage area and injuries improved eventually. Conclusion: Based on these cases, supplementation with equine placenta extract may be an effective treatment option for ocular conditions that are difficult to treat surgically.

Sphingolipid-Enriched Porcine Placental Extract Promotes the Expression of Structural Genes and Desquamation Enzyme Genes in Cultured Human Keratinocytes.

Porcine placental extract (PPE) is commonly used in various health foods and cosmetics. PPE use in cosmetics predominantly consist of the water-soluble fraction derived from the entire placenta. In this report, we examined the effect of the hydrophobic constituents of the PPE, specifically the sphingolipid-enriched fraction designated as the sphingolipid-enriched porcine placental extract (SLPPE), on the expression of genes associated with skin function in cultured normal human epidermal keratinocytes. Using quantitative RT-PCR (qRT-PCR) analysis, we found that SLPPE concentrations ranging from 25 to 100 µg/mL upregulated the gene expression of key components associated with the cornified envelope structure (filaggrin (FLG), involucrin (IVL) and loricrin (LOR)), cornification enzymes (transglutaminase 1 (TGM1) and TGM5) and the desquamation enzymes (kallikrein 5 (KLK5) and KLK7). Additionally, KLK5p and FLG protein (FLGp) were detected in the culture supernatants of keratinocytes treated with SLPPE at these concentrations. These findings suggest that SLPPE is possible to promote the cornification and desquamation in epidermal keratinocytes, and it may offer potential benefits in cosmetics.

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.

Placental extract suppresses lipid droplet accumulation by autophagy during the differentiation of adipose-derived mesenchymal stromal/stem cells into mature adipocytes.

OBJECTIVE: Placental extract, which contains various bioactive compounds, has been used as traditional medicine. Many studies have demonstrated additional applications of placental extract and provided a scientific basis for the broad spectrum of its effects. We have previously reported that porcine placental extract (PPE) strongly suppresses adipogenesis in a 3T3-L1 preadipocyte cell line, inhibiting differentiation. This study aimed to examine the effect of PPE on the accumulation of lipid droplets (LD) in adipose-derived mesenchymal stromal/stem cells (ASC). RESULTS: The study findings revealed that PPE decreased the size of LD during the differentiation of ASC into mature adipocytes. RT-qPCR analysis revealed that PPE increased the gene expression of lysosomal acid lipase A (Lipa), a lipolysis-related gene, in ASC-differentiated adipocytes. However, no differences were noted in the adipocyte differentiation markers (Pparg, Cebpa, and Adipoq), or the adipogenesis-related genes (Dgat1, Dgat2, Fasn, Soat1, and Soat2). In addition, PPE promoted autophagosome formation, which was partially co-localized with the LD, indicating that PPE accelerated the degradation of LD by inducing autophagy (termed lipophagy) during the differentiation of ASC into mature adipocytes. These results suggest that the use of PPE may be a potential novel treatment for regulating adipogenesis for the treatment of obesity.

Effect of autologous bone marrow derived mesenchymal stem cells in treatment of rheumatoid arthritis.

INTRODUCTION: Chronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA. AIM OF THE STUDY: This study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats. MATERIALS AND METHODS: In female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out. RESULTS: Combining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE. CONCLUSION: The combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.

Successful steroid tapering and partial treatment of suspected immune-mediated haemolytic anaemia in a dog with equine placenta extract supplementation: A case report.

Background: We report on the clinical management and outcome of an 11-year-old dog diagnosed with suspected refractory immune-mediated anemia (IMHA) and treated with equine placental extract supplementation. Case Description: The patient had received standard treatment with subcutaneous infusion of prednisone (2 mg/kg) and oral administration (1.3 mg/kg semel in die [sid]), with limited success as hematocrit (HCT) values continued to fall rapidly, and the patient continued to have severe symptoms of fatigue. The patient was then put on equine placental extract supplements, after which the patient's physical exhaustion was improved, and although the HCT level initially continued to fall, it eventually began to rise and remained near normal for approximately 2 years. A significant reduction in prednisone use was achieved with placental supplementation. Conclusion: Equine placental supplementation may be useful as a new complementary therapy for suspected refractory IMHA.

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.

Porcine placental extract increase the cellular NAD levels in human epidermal keratinocytes.

Nicotinamide adenine dinucleotide (NAD) is an essential cofactor for numerous enzymes involved in energy metabolism. Because decreasing NAD levels is a common hallmark of the aging process in various tissues and organs, maintaining NAD levels has recently been of interest for the prevention of aging and age-related diseases. Although placental extract (PE) are known to possess several anti-aging effects, the NAD-boosting activity of PE remains unknown. In this study, we found that porcine PE (PPE) significantly increased intracellular NAD levels in normal human epidermal keratinocytes (NHEKs). PPE also attenuated the NAD depletion induced by FK866, an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT). Interestingly, only the fraction containing nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) restored NAD content in NHEKs in the absence of NAMPT activity. These results suggest that PPE increases intracellular NAD by providing NAD precursors such as NMN, NR, and NAM. Finally, we showed that the application of PPE to the stratum corneum of the reconstructed human epidermis significantly ameliorated FK866-induced NAD depletion, suggesting that topical PPE may be helpful for increasing skin NAD levels. This is the first study to report the novel biological activity of PE as an NAD booster in human epidermal cells.

Equine placental extract supplement as a night barking remedy in dogs with cognitive dysfunction syndrome.

With the aging of pet dogs, there has been an increasing trend in senility-related diseases; additionally, cognitive disorders accompanied by abnormal behaviours are a major burden for owners. Recently, there have been a series of consultations regarding the fact that night barking, which is an abnormal behaviour, remarkably interferes with the owner's sleep and adversely affects the owner's quality of life. However, there has been no effective solution to this problem. In this study, three aged pet dogs diagnosed with dementia were administered an equine placental extract (eqPE) as pet supplement, which has been shown in laboratory models to improve cognitive function. Consequently, night barking ceased 1 week after the administration of eqPE in case 2 and it was observed to decrease in the other two dogs. Furthermore, night barking disappeared 2 and 3 weeks after the administration of eqPE in cases 1 and 3, respectively. No recurrence or exacerbation of night barking was observed in the three cases treated with the eqPE, and no adverse events were observed. These results suggest that eqPE may be useful for improving night barking in pet dogs with dementia, and it is expected to be a new treatment method.

Vanillin reduction in the biosynthetic pathway of capsiate, a non-pungent component of Capsicum fruits, is catalyzed by cinnamyl alcohol dehydrogenase.

Capsicum fruits synthesize capsaicin from vanillylamine, which is produced from vanillin in a reaction catalyzed by a putative aminotransferase (pAMT). Capsiate, a non-pungent compound that is structurally similar to capsaicin, is synthesized from vanillyl alcohol rather than vanillylamine. Vanillyl alcohol is possibly generated by the enzymatic reduction of vanillin, but the enzyme responsible for this reaction is unknown. In the present study, we revealed that the vanillin reductase in the capsiate biosynthetic pathway is cinnamyl alcohol dehydrogenase (CAD), which is an enzyme involved in lignin synthesis. The reduction of vanillin to vanillyl alcohol was greater in the mature red fruit placental extract than in the immature green fruit placental extract. This reduction was suppressed by both N-(O-hydroxyphenyl) sulfinamoyltertiobutyl acetate, a specific inhibitor of CAD, and ethylenediaminetetraacetic acid, a metalloenzyme inhibitor. The CaCAD1 transcript levels in the placenta were higher in the red fruits than in the green fruits. A recombinant CaCAD1 protein obtained using an Escherichia coli expression system reduced vanillin to vanillyl alcohol. This reaction was suppressed by the CAD inhibitors. These results strongly suggest that CAD is the enzyme that catalyzes the reduction of vanillin to vanillyl alcohol during capsiate biosynthesis. Syntenic analyses indicated that genes encoding CAD and capsaicin synthase (Pun1) involved in capsiate biosynthesis were acquired before the pAMT gene during the evolution of the family Solanaceae. This raises the possibility that in the genus Capsicum, the capsiate biosynthetic pathway emerged before the pAMT-encoding gene was acquired as the final trigger for capsaicin biosynthesis.

Highly elastic 3D-printed gelatin/HA/placental-extract scaffolds for bone tissue engineering.

Bioengineering scaffolds have been improved to achieve efficient regeneration of various damaged tissues. In this study, we attempted to fabricate mechanically and biologically activated 3D printed scaffold in which porous gelatin/hydroxyapatite (G/H) as a matrix material provided outstanding mechanical properties with recoverable behavior, and human placental extracts (hPE) embedded in the scaffold were used as bioactive components. Methods: Various cell types (human adipose-derived stem cells; hASCs, pre-osteoblast; MC3T3-E1, human endothelial cell line; EA.hy926, and human dermal fibroblast; hDFs) were used to assess the effect of the hPE on cellular responses. High weight fraction (~ 70 wt%) of hydroxyapatite (HA) in a gelatin solution supplemented with glycerol was used for the G/H scaffold fabrication, and the scaffolds were immersed in hPE for the embedding (G/H/hPE scaffold). The osteogenic abilities of the scaffolds were investigated in cultured cells (hASCs) assaying for ALP activity and expression of osteogenic genes. For the in vivo test, the G/H and G/H/hPE scaffolds were implanted in the rat mastoid obliteration model. Results: The G/H/hPE scaffold presented unique elastic recoverable properties, which are important for efficient usage of implantable scaffolds. The effects of G/H and G/H/hPE scaffold on various in vitro cell-activities including non-toxicity, biocompatibility, and cell proliferation were investigated. The in vitro results indicated that proliferation (G/H = 351.1 ± 13.3%, G/H/hPE = 430.9 ± 8.7% at day 14) and expression of osteogenic markers (ALP: 3.4-fold, Runx2: 3.9-fold, BMP2: 1.7-fold, OPN: 2.4-fold, and OCN: 4.8-fold at day 21) of hASCs grown in the G/H/hPE scaffold were significantly enhanced compared with that in cells grown in the G/H scaffold. In addition, bone formation was also observed in an in vivo model using rat mastoid obliteration. Conclusion:In vitro and in vivo results suggested that the G/H/hPE scaffold is a potential candidate for use in bone tissue engineering.

Human placental extract activates a wide array of gene expressions related to skin functions.

As skin aging is one of the most common dermatological concerns in recent years, scientific research has promoted treatment strategies aimed at preventing or reversing skin aging. Breakdown of the extracellular matrix (ECM), such as collagen and elastin fibers, in the skin results in decreased skin elasticity and tension. Cutaneous cells, especially fibroblasts in the dermis layer of the skin, mainly produce ECM proteins. Although clinical studies have demonstrated that placental extract (PE) has positive effects on skin health, the molecular mechanisms by which PE acts against skin aging are still largely unknown. In this study, we performed RNA-sequence analysis to investigate whether human PE (HPE) alters ECM-related gene expression in normal human dermal fibroblast (NHDF) cells. Gene ontology analysis showed that genes related to extracellular matrix/structure organization, such as COL1A1, COL5A3, ELN, and HAS2 were highly enriched, and most of these genes were upregulated. We further confirmed that the HPE increased the type I collagen, proteoglycan versican, elastin, and hyaluronan levels in NHDF cells. Our results demonstrate that HPE activates global ECM-related gene expression in NHDF cells, which accounts for the clinical evidence that the HPE affects skin aging.

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.

Placental extract suppresses the formation of fibrotic deposits by tumor necrosis factor alpha and transforming growth factor beta-induced epithelial-mesenchymal transition in ARPE-19 cells.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) is involved in the development of proliferative vitreoretinopathy (PVR) and subsequent fibrosis. Previously, we demonstrated that placental extract ameliorates fibrosis in a mouse model of non-alcoholic steatohepatitis. In this study, we evaluated whether placental extract influences EMT and fibrosis through cytokine-induced EMT in the retinal pigment epithelial cells, in vitro. RESULTS: Placental extract did not inhibit EMT, but it suppressed excessive mesenchymal reactions and the subsequent fibrosis. These results suggest that placental extract effectively ameliorates EMT-associated fibrosis in PVR. This beneficial effect could be partially attributed to the suppression of excessive mesenchymal reactions.

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)

Human placental extract ameliorates methotrexate-induced hepatotoxicity in rats via regulating antioxidative and anti-inflammatory responses.

PURPOSE: Methotrexate (MTX) induces hepatotoxicity, limiting its clinical efficacy as a widely known chemotherapy drug. In the current study, we examined the protective effect of human placenta extract (HPE) against MTX-induced liver damage in rats, as well as its ability to regulate antioxidative and anti-inflammatory liver responses. METHODS: Male rats were orally administered MTX at a daily dose of 5 mg/kg-body-weight in the presence or absence of HPE (10.08 mg/kg) for 2 weeks. We measured the biological effects of MTX and HPE on the levels of liver enzymes, lipid profile, lipid peroxidation, oxidative stress biomarkers, and cytokines [tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)]. In addition, histological examination and histopathological scoring of liver tissues were performed. RESULTS: MTX-treated rats showed significantly increased (p < 0.001) liver enzyme levels for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), total bilirubin, total cholesterol, and triglyceride levels. However, HPE supplementation in MTX-treated rats significantly decreased (p < 0.001) these elevated levels. HPE supplementation also significantly reduced the oxidative stress biomarker malondialdehyde (MDA), reversed the reduction in glutathione (GSH), and markedly increased the antioxidant enzyme activities of catalase (CAT) and superoxide dismutase (SOD) in the livers of MTX-treated rats. Furthermore, HPE supplementation significantly decreased the MTX-elevated levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-10. Histopathological examinations showed that MTX produced severe cellular damage and inflammatory lesions in liver tissues, while treatment with HPE improved hepatic histologic architecture. CONCLUSION: HPE has the ability to ameliorate methotrexate-induced liver injury in rats by mechanisms that include boosting antioxidative responses and down-regulating MDA and pro-inflammatory cytokine production.

Therapeutic Effect of Murine Bone Marrow-Derived Mesenchymal Stromal/Stem Cells and Human Placental Extract on Testicular Toxicity Resulting from Doxorubicin in Rats.

Oncotherapeutics like doxorubicin can affect male gonads; as a result, it leads to infertility. This work was conducted to demonstrate the toxic effects of doxorubicin on testes of male albino rats. Fifty male albino rats aged 5-7 weeks were used in this study. The animals were randomly separated into 5 sets (each set containing ten rats). Group I received saline (i.p.) for 4 weeks. Group II was given doxorubicin (DOX), 5 mg/kg BW (i.p.) once/week for 4 weeks. Groups III and IV were treated in the same way as the DOX group, left for one week without medication, and then injected with mesenchymal stromal cells (MSCs) or human placental extract (HPE) therapy in a single dose of 5 × 106 in 200 ml PRP/week or 40 µl placental extract for 4 weeks via the caudal vein. Group V rats were treated in the same way as the DOX group also, left for one week without medication, and then injected with MSC+HPE. A significant decrease in serum testosterone, FSH, and LH levels was observed in rats treated with DOX compared to the control group. A significant elevation was recorded in rats treated with DOX+MSC or DOX+HPE when compared with the DOX group only. Rats that were given MSC+HPE after DOX intoxication showed a significant increase in hormone levels when compared to rats treated with either MSC or HPE. Light and electron microscopic examinations revealed that DOX intoxication initiated degenerative and necrotic changes in seminiferous tubules associated with partial or complete cessation of spermatogenesis. These effects were reversed by the effect of MSC or HPE. Coadministration of MSC and HPE even showed further improvement. Finally, we can say that doxorubicin has a deleterious impact on rat testes; however, therapeutic effects can be induced through MSC and/or HPE administration.

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.