Investigating the traditional medicine shoulder pain (Jian Tong) characteristics in patients with ischaemic stroke in the early rehabilitation phase.

Introduction: Ischaemic stroke often leaves serious sequelae affecting patients' daily activities and quality of life, especially shoulder pain. Shoulder pain after stroke often occurs in the first 3 months with an occurrence rate of 25-72% due to the strong natural neurological mechanism during the time, interferes with the recovery of motor function, increases hospital stay, is associated with depression, and limits mobility as well as inhibits treatment results. In Vietnam, Traditional Medicine (TM) has played an essential role in treating and rehabilitating shoulder pain after stroke for quite a long time. Studies on the pathology of shoulder pain (Jian Tong) after stroke in TM in Vietnam are still inadequate. Therefore, this study evaluated the severity and characteristics of post-stroke Jian Tong in patients with ischaemic stroke. Methods: The study was conducted from January 1, 2023-May 1, 2023. The study consisted of two phases: Phase 1: Searching TM documents and selecting the characteristics that appear in the documents as components for the questionnaire of phase 2. Phase 2: Conduct a cross-sectional study to investigate the characteristics of Jian Tong in 65 patients after ischaemic stroke in the early rehabilitation phase. Results: In phase 1, the study encoded 17 features of Jian Tong from 10 literary documents. In phase 2, we surveyed over 65 patients, and the result was that shoulder pain aggravated by exertion had the highest rate, whereas shoulder pain alleviated by cold and distended shoulder had the fewest. Pain level measured by Number Rating Scale (NRS) points and gender was significantly related to the characteristics of TM shoulder pain - Jian Tong (p < 0.05). Conclusion: The study demonstrated the pain level and the characteristics of Jian Tong in patients with ischaemic stroke in the early rehabilitation phase to contribute to the process of personalized diagnosing and treating Jian Tong after stroke for each patient, especially based on the theoretical basis and reasoning methods of Traditional Medicine.

Identification, Phytochemistry and Biological Activities of Paris polyphylla on Hepatocellular Carcinoma.

<b>Background and Objective:</b> Liver cancer is the common cause of cancer death. <i>Paris polyphylla</i> is used as a traditional folk medicine in Vietnam to treat pneumonia, mastitis, bruises and fractures but no study was available regarding its ability to treat liver cancer or slow its growth. In this study, <i>Paris polyphylla</i> samples were identified and evaluated cytotoxic activity against the liver cancer cells. <b>Materials and Methods:</b> <i>Paris polyphylla</i> species were collected from various areas in Yen Bai, Vietnam, which were identified by comparative morphological method and DNA barcoding for the <i>18S, matK</i> genes and <i>ITS</i> region. <i>Paris polyphylla</i> samples were dried until constant weight, ground into a fine powder and extracted in various solvents. The bioactivity of these extracts were done by the MTT assay. <b>Results:</b> The sequences of <i>18S, matK</i> genes and <i>ITS</i> region were high similarity to sequences of <i>P. polyphylla</i> in the National Center for Biotechnology Information. The N-hexane and ethyl acetate fractions were produced from the methanol extract of <i>P. polyphylla</i>. The TLC results showed that there was a significant difference in the component of n-hexane and ethyl acetate fraction. The N-hexane fraction contains mainly low-polarity and non-polarity substances. While ethyl acetate fraction consists mainly of polar substances. In addition, ethyl acetate fraction was shown the strongest cytotoxic activity on the cancer cell lines HepG2 and Huh7 with the evaluation of IC₅₀ = 115.11±2.77 µg mL¹ and IC₅₀ = 148.11±1.78 µg mL¹. <b>Conclusion:</b> The extract of <i>Paris polyphylla</i> demonstrated strong potential to inhibit the growth of the liver cancer cell line. The ethyl acetate fraction has the highest ability for cytotoxicity on the liver and cell line at a concentration of 200 µg mL¹ through MTT.

Sorafenib as first-line treatment for patients with primary hepatocellular carcinoma: an outcome evaluation.

OBJECTIVE: To evaluate the clinical outcomes following first-line treatment with sorafenib in patients with primary hepatocellular carcinoma (HCC). METHODS: This retrospective cohort study enrolled patients with primary HCC that had been treated with sorafenib. Their data were collected from the hospital medical records database at three time-points: after three cycles, after six cycles and at the end of the sorafenib treatment regimen. The starting dose was 800 mg/day sorafenib but this could be reduced to 600 mg/day or 400 mg/day if patients developed adverse events (AEs). RESULTS: A total of 98 patients participated in the study. Of these, nine (9.2%) had a partial response, 47 patients (48.0%) had stable disease and 42 patients (42.9%) had progressive disease. The overall disease control rate was 57.1% (56 of 98 patients). Median progression-free survival for the overall cohort was 4.7 months. The most common AEs were hand-foot skin reaction (49 of 98 patients; 50.0%), fatigue (41 of 98 patients; 41.8%), appetite loss (39 of 98 patients; 39.8%) and hepatotoxicity/transaminitis (24 of 98 patients; 24.5%). The majority of the AEs were toxicity grades 1 and 2. CONCLUSION: Sorafenib as a first-line treatment for primary HCC patients provided survival benefits and the AEs were well tolerated by patients.

Neuroprotective effects of total alkaloids fraction of Huperzia serrata on scopolamine-induced neurodegenerative animals.

Huperzia serrata contains Huperzine A (HupA)-an alkaloid used to treat cognitive dysfunction. In this study, we used the total alkaloids (HsAE) to investigate their potential in managing cognitive impairment in comparison with HupA. The antioxidant activity was measured by DPPH assay. In the cellular study, the cell viability and level of ACh of SH-SY5Y cells were evaluated after pretreated with HsAE and scopolamine. For in vivo assay, mice were pre-treated with HsAE, and HupA and undergone scopolamine injection for cognitive impairment. The behavioral tests including the Y-maze and Morris water maze test and the AChE activity, the SOD, CAT, MDA level in the hippocampus and cortex were evaluated. HsAE showed significant scavenging properties on DPPH radicals. HsAE was not toxic to SH-SY5Y cells, and can rescue these cells upon scopolamine treatment. Intriguingly, HsAE showed the neuroprotection against scopolamine-induced amnesia in mice. Moreover, HsAE decreased AChE activity, MDA level, increased antioxidative enzyme activity in the hippocampus as well as cortex of mice, which was relatively better than that of HupA. These findings suggested that HsAE may significantly protect the neurons of mice with scopolamine-induced memory impairment connected to AChE depletion and oxidative stress.

Surface-enhanced Raman scattering (SERS) from low-cost silver nanoparticle-decorated cicada wing substrates for rapid detection of difenoconazole in potato.

Potato is one of the most important food crops worldwide in terms of human consumption. However, potato farmers employ a variety of pesticides to protect crops from harmful insects and illnesses, and difenoconazole is a commonly used one that has severe effects on human health and the environment. Therefore, detecting difenoconazole quickly and correctly is critical. In this work, we fabricated AgNPs/cicada wing substrates using natural cicada segments, decorated with silver nanoparticles for surface-enhanced Raman scattering (SERS) measurements to detect trace amounts of difenoconazole in potatoes. Results indicated that a linear relationship with the coefficient of detection (R2) of 0.987 and the detection limit (LOD) of 0.016 ppm was observed by targeting a distinctive peak at 808 cm-1 and logarithmic difenoconazole concentrations of 0.1 to 100 ppm. In addition, difenoconazole LODs in potatoes were 63 µg/kg, lower than those specified by the EU (0.1 mg/kg) and Vietnam (4 mg/kg) utilizing this new technique. Therefore, this proposed SERS method could be used to detect difenoconazole in potatoes at trace levels.

pH-dependent ileocolonic drug delivery, part II: preclinical evaluation of novel drugs and novel excipients.

Novel drugs and novel excipients in pH-dependent ileocolonic drug delivery systems have to be tested in animals. Which animal species are suitable and what in vivo methods are used to verify ileocolonic drug delivery?

The Homeodomain Transcription Factors Vax1 and Six6 Are Required for SCN Development and Function.

The brain's primary circadian pacemaker, the suprachiasmatic nucleus (SCN), is required to translate day-length and circadian rhythms into neuronal, hormonal, and behavioral rhythms. Here, we identify the homeodomain transcription factor ventral anterior homeobox 1 (Vax1) as required for SCN development, vasoactive intestinal peptide expression, and SCN output. Previous work has shown that VAX1 is required for gonadotropin-releasing hormone (GnRH/LHRH) neuron development, a neuronal population controlling reproductive status. Surprisingly, the ectopic expression of a Gnrh-Cre allele (Gnrhcre) in the SCN confirmed the requirement of both VAX1 (Vax1flox/flox:Gnrhcre, Vax1Gnrh-cre) and sine oculis homeobox protein 6 (Six6flox/flox:Gnrhcre, Six6Gnrh-cre) in SCN function in adulthood. To dissociate the role of Vax1 and Six6 in GnRH neuron and SCN function, we used another Gnrh-cre allele that targets GnRH neurons, but not the SCN (Lhrhcre). Both Six6Lhrh-cre and Vax1Lhrh-cre were infertile, and in contrast to Vax1Gnrh-cre and Six6Gnrh-cre mice, Six6Lhrh-cre and Vax1Lhrh-cre had normal circadian behavior. Unexpectedly, ~ 1/4 of the Six6Gnrh-cre mice were unable to entrain to light, showing that ectopic expression of Gnrhcre impaired function of the retino-hypothalamic tract that relays light information to the brain. This study identifies VAX1, and confirms SIX6, as transcription factors required for SCN development and function and demonstrates the importance of understanding how ectopic CRE expression can impact the results.

Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization.

Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.

Engineering a Brain Cancer Chip for High-throughput Drug Screening.

Glioblastoma multiforme (GBM) is the most common and malignant of all human primary brain cancers, in which drug treatment is still one of the most effective treatments. However, existing drug discovery and development methods rely on the use of conventional two-dimensional (2D) cell cultures, which have been proven to be poor representatives of native physiology. Here, we developed a novel three-dimensional (3D) brain cancer chip composed of photo-polymerizable poly(ethylene) glycol diacrylate (PEGDA) hydrogel for drug screening. This chip can be produced after a few seconds of photolithography and requires no silicon wafer, replica molding, and plasma bonding like microfluidic devices made of poly(dimethylsiloxane) (PDMS). We then cultured glioblastoma cells (U87), which formed 3D brain cancer tissues on the chip, and used the GBM chip to perform combinatorial treatment of Pitavastatin and Irinotecan. The results indicate that this chip is capable of high-throughput GBM cancer spheroids formation, multiple-simultaneous drug administration, and a massive parallel testing of drug response. Our approach is easily reproducible, and this chip has the potential to be a powerful platform in cases such as high-throughput drug screening and prolonged drug release. The chip is also commercially promising for other clinical applications, including 3D cell culture and micro-scale tissue engineering.

Profiling flavonoid cytotoxicity in human breast cancer cell lines: determination of structure-function relationships.

Flavonoids have been shown to be cytotoxic to cancer cells. However, the mechanism of cytotoxicity has not been clearly defined. It has previously been reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53 were required for flavonoid induced cytotoxicity in breast cancer cell lines. We have used a panel of breast cancer cell lines, known to contain as well as be deficient in these signaling pathways, to screen fourteen different flavonoids. Comparing the cytotoxicity for all flavonoids allows us to determine if a structure-functional relationship exists between cytotoxicity and flavonoid, and if a particular signaling pathway is required for cytotoxicity. We show that several flavonoids are cytotoxic to all cell lines including primary mammary epithelial cells tested. The cytotoxic flavonoids are also able to inhibit Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP levels whereas the non-cytotoxic flavonoids are not able to do this. We also show that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless of their cytotoxicity were able to induce some form of cell cycle arrest. We conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3-double bond in the C-ring and we believe the cytotoxicity occurs through mitochondrial poisoning in both cancer and normal cells.

Profiling flavonoid cytotoxicity in human breast cancer cell lines: determination of structure-function relationships.

Flavonoids have been shown to be cytotoxic to cancer cells. However, the mechanism of cytotoxicity has not been clearly defined. It has previously been reported that HER2/ERBB2, the estrogen receptor, progesterone receptor, and p53 were required for flavonoid induced cytotoxicity in breast cancer cell lines. We have used a panel of breast cancer cell lines, known to contain as well as be deficient in these signaling pathways, to screen fourteen different flavonoids. Comparing the cytotoxicity for all flavonoids allows us to determine if a structure-functional relationship exists between cytotoxicity and flavonoid, and if a particular signaling pathway is required for cytotoxicity. We show that several flavonoids are cytotoxic to all cell lines including primary mammary epithelial cells tested. The cytotoxic flavonoids are also able to inhibit Mitochondrial Outer Membrane Permeability while at the same time stimulate ATP levels whereas the non-cytotoxic flavonoids are not able to do this. We also show that both cytotoxic and non-cytotoxic flavonoids can transverse the cell membrane to enter MDA-MB-231 cells at different levels. Finally, all flavonoids regardless of their cytotoxicity were able to induce some form of cell cycle arrest. We conclude that for flavonoids to be strongly cytotoxic, they must possess the 2,3-double bond in the C-ring and we believe the cytotoxicity occurs through mitochondrial poisoning in both cancer and normal cells.