Therapeutic potential of Thai herbal formula for cognitive impairment: A metabolomics approach for Comprehensive Insights.

Chronic cerebral ischemia hypoperfusion plays a role in the initiation and progression of vascular dementia, which causes changes in metabolites. Currently, there is no standard treatment to treat, prevent and reduce the severity of this condition. Thai herbal Yahom no.20 (YHF20) is indicated for fatigue and dizziness. The components of YHF20 have been found to have pharmacological effects related to the pathology of chronic cerebral ischemia hypoperfusion. This study aimed to investigate metabolomic changes after YHF20 administration in a rat model of permanent bilateral common carotid artery occlusion (2-VO) induced chronic cerebral ischemia hypoperfusion, and to explore its impact on spatial learning and memory. Albino Wistar rats were randomly allocated to 5 groups; sham, 2-VO, 2-VO+ 100 mg/kg YHF20, 2-VO+300 mg/kg YHF20, and 2-VO+1000 mg/kg YHF20. The rats were administered YHF20 daily by oral gavage for 56 days after 2-VO induction. Plasma was collected weekly for metabolome change analysis using LC-MS/QTof and toxicity study. The rats were evaluated for spatial learning and memory using the Morris water maze. The results showed that 78 known metabolites and 10 tentative pathways altered after chronic cerebral hypoperfusion, although it was not able to determine the effect on memory and learning behaviors of rats. Glutathione and glutathione metabolism might be metabolite-pathway that were the affect after YHF20 administration in cerebral ischemic condition. The 4 known metabolites may be the metabolites from the constituents of YHF20 could be considered and confirmed for quality control purpose. In conclusion, YHF20 administration might contribute to metabolic changes related to cerebral ischemia condition without the effect on spatial learning and memory, including hepatotoxicity and nephrotoxicity after 56 days of treatment. Alterations in the potential metabolites may provide data support for elucidating dementia pathogenesis and selecting pathways for intervention.

Spatiotemporally differential expression of HER (human epithelial growth factor receptor)-2 with sexual dimorphism in submandibular gland of mice

SUMMARY: Considering that the submandibular gland (SMG) of postnatal mice performs active cell proliferation, apoptosis and differentiation which are regulated by proto-oncogene products in cancerous cells, the expression and localization of a proto-oncogene product HER (human epidermal growth factor receptor)-2 was examined in SMG of postnatal mice. In Western blot analysis, the expression for HER-2 was high until pre-puberty, and it decreased from puberty to young adult stages with male SMG more dominant. In immunohistochemistry, the immunoreactivity was positive in acinar and ductal cells of newborn SMG with distinct localization at the intercellular apposition sites. The immunoreactivity in acinar cells progressively decreased to negligible levels by pre-pubertal stage, while it remained positive in most ductal cells throughout the postnatal time-course. The immunoreactivity in cells of terminal tubules and intercalated ducts, both of which have a high potential to produce cells, were seen at levels similar to those of more proximal ducts, while the immunoreactivity in ductal basal cells was significantly high, but the granular convoluted tubule cells were seen at negligible levels in male and at faint levels in female. In immuno-electron microscopy of excretory ducts, the immunoreactivity was dominantly localized on the basal infolding membranes as well as vesicles and vacuoles of various sizes, but rarely in Golgi apparatus and mitochondria. The immunoreactivity without association to any membranous structures were also seen, though not numerous. The relation of expression levels of HER-2 in various portions of normal SMG to those in their cancerous ones is briefly discussed.

RESUMEN: Considerando que la glándula submandibular (GSM) de ratones postnatales realiza la proliferación celular activa, apoptosis y diferenciación que están reguladas por productos protooncogénicos en células cancerosas, la expresión y localización de un producto protooncogénico HER (receptor del factor de crecimiento epidérmico humano) - 2 se examinó en GSM de estos ratones. En el análisis de Western blot, la expresión de HER-2 fue alta hasta la prepubertad, y disminuyó desde la pubertad hasta las etapas de adultos jóvenes con GSM macho más dominante. En inmunohistoquímica, la inmunorreactividad fue positiva en las células acinares y ductales de GSM de recién nacido con una localización distinta en los sitios de aposición intercelular. La inmunorreactividad en las células acinares disminuyó progresivamente a niveles insignificantes en la etapa prepuberal, mientras que permaneció positiva en la mayoría de las células ductales durante el transcurso del tiempo posnatal. La inmunorreactividad en las células de los túbulos terminales y los conductos intercalados, los cuales tienen un alto potencial para producir células, se obser- vó a niveles similares a los de los conductos más proximales, mientras que la inmunorreactividad en las células basales ductales fue significativamente alta, pero en el túbulo contorneado granular las células se observaron en niveles insignificantes en los machos y en niveles débiles en las hembras. En la microscopía inmunoelectrónica de los conductos excretores, la inmunorreactividad se localizó de manera predominante en las membranas de pliegues basales, así como en vesículas y vacuolas de varios tamaños, pero raramente en el aparato de Golgi y en las mitocondrias. También se observó la inmunorreactividad sin asociación a ninguna estructura membranosa, aunque no numerosa. Se discute brevemente la relación de los niveles de expresión de HER-2 en varias porciones de GSM normal con aquellos en sus cancerosos.

Efficacy of chitin-PAA-GTMAC gel in promoting wound healing: animal study.

Acrylic grafted chitin (chitin-PAA) was modified with glycidyltrimethylammonium chloride (GTMAC) with the aim of promoting wound healing. The chitin-PAA-GTMAC gels with different GTMAC contents were compared with the original chitin-PAA gel and Intrasite gel for their efficacy in deep wound healing of Wistar rats. Four full-thickness wounds were made on the dorsal skin of rats and then each was treated with 4 materials; chitin-PAA, chitin-PAA-GTMAC(1:4), chitin-PAA-GTMAC(1:10) and Intrasite gel. During 18 days of treatment, the wounds were visually observed and calculated for wound size using image analysis program. Skin wound tissues of sacrificed rats were processed for routine histological observation and immunohistochemistry of proliferating cell nuclear antigen (PCNA). The wounds covered with the chitin derivatives either with or without GTMAC showed a significant reduction in wound size in day 9 in comparison with day 12 for those covered with Intrasite gel. The faster rate and the better pattern of epidermal development observed in histological study as well as the higher dermal cell proliferation (PCNA expression) also demonstrated the better efficiency in wound healing of the chitin derivatives than Intrasite. The earliest epidermal development of the wounds treated with chitin-PAA-GTMAC (1:4) among the tested materials suggested the most promising of this material for the treatment of full-thickness open wound.

A histopathological study of hearts and spleens of hamsters (Mesocricetus auratus) infected with Leptospira interrogans, serovar pyrogenes.

The effects of Leptospira interrogans on the heart and spleen of hamsters were studied histopathologically. Infected hamsters were sacrificed at 1 hour, 6 hours and on days 1, 2, 3, 4, 5 and 6 after inoculation with Leptospira interrogans serovar pyrogenes. The heart and spleen of each of the sacrificed animals were removed and processed for routine conventional light microscopy. Infected hearts showed degenerative change of the cardiac muscle cells composed of cellular swelling, condensation of chromatin granules, pyknotic nuclei and acidophilic cytoplasm. Congestion of the cardiac blood vessels and hemorrhagic areas were found. Necrosis of the cardiac muscle cells was surrounded by numerous inflammatory cells. In the spleen, cellular necrosis was found scattered throughout the splenic cord. The splenic sinusoids were dilated and congested with many hemorrhagic areas. Inflammatory cell infiltration was also noted in the splenic parenchyma and the splenic sinusoids.

The ultrastructure of the gravid uterus of Brugia pahangi, another rich source of antigen of the filarial parasite.

The gravid uterus with zygotes and microfilariae in utero of Brugia pahangi, a rich source of antigen as revealed by a recent immunofluorescent technique, were studied ultrastructurally. The epithelial cells of uterus show ultrastructural features of synthetically active cells. Their secretions may provide nutrients for the egg in utero. On the basal side, the uterine epithelial cells may also secrete substances to form the basal lamina of the uterus which is rather thick and irregularly fused with the basal lamina lining the body wall where the pseudocoelomic cavity is obliterated. For the most part, the uterine basal lamina contains uniform granular material of moderate electron density. There are also elongated visceral muscle cells embeded in it, and which surround the uterus, with adjacent cells overlapping. The gravid uterus contains several stages of developing microfilariae within its lumen, the cleaving zygotes are also present at another level. The morula of zygotes are composed of several closely packed cells surrounded loosely by their own egg shell membranes. The egg shell becomes more convoluted as development proceeds. The egg shell surrounding the developing microfilariae in utero is secreted by the uterine epithelium. This structure later becomes the sheath of circulating microfilariae, and is highly antigenic as indicated by intense labeling with fluorescent antibodies.