Bullous hemorrhagic dermatosis (BHD) is a rare cutaneous manifestation characterized by tense hemorrhagic bullae that appear at sites distant from low molecular weight heparin (LMWH) injections, typically within seven days of exposure. As of March 2022, only 94 cases have been reported. It most commonly affects elderly males with predisposing factors for thromboembolism, such as carcinoma, and usually involves the extremities.

This case highlights the importance of maintaining a high index of suspicion for bullous hemorrhagic dermatosis (BHD) in patients receiving low molecular weight heparin, even beyond the typical 7-day window and in demographics not commonly affected. Early recognition and prompt discontinuation of the offending agent, as demonstrated in this atypical presentation involving a Filipino elderly woman with multiple comorbidities and no malignancy, can lead to favorable outcomes. Clinicians should be aware of this rare but reversible complication to avoid misdiagnosis and ensure appropriate management.

Human ; Female ; Aged: 65-79 Yrs Old ; Affect ; Aged ; Blister ; Carcinoma ; Causality ; Demography ; Diagnostic Errors ; Enoxaparin ; Extremities ; Heparin ; Heparin, Low-molecular-weight ; Index ; Injections ; Lead ; Male ; Molecular Weight ; Neoplasms ; Patients ; Research Report ; Skin Diseases ; Thromboembolism ; Women

BACKGROUND

The COVID-19 pandemic caused by SARS-CoV-2 significantly strained healthcare systems in the Philippines, highlighting the critical importance of reliable molecular diagnostics and genomic surveillance. Although vaccination efforts and public health measures mitigated disease impact, the continued emergence of viral variants underscores the need for sustainable local surveillance strategies. Strengthening in-country capacity through the development of in silico–designed primers and cost-effective sequencing approaches can enhance rapid variant detection and improve preparedness for future emerging infectious diseases.

OBJECTIVE

This paper offers a method in detecting the SARS-CoV-2 virus and its variants. A direct PCR product sequencing surveillance or DPPSS offers a new possibility of detecting emerging disease by using PCR products and using it as templates in determining the base sequence.

METHODOLOGY

A total of 20 random positive samples for SARS-COV-2 from March 2022 sample pool in Metro Manila, Philippines was used in this study. The RNA was extracted using Purelink™ RNA Mini Kit, quantified with NanoDrop, and subjected to one-step RT-PCR. An in-house designed in silico primers were used in this study by using thermodynamic parameters to optimize specificity and amplification efficiency, considering GC contents, balanced Tm, minimal secondary structures and cross-dimers and in silico validation via Basic Local Alignment Search Tool (BLAST) against reference databases.

Amplicons were analyzed through gel electrophoresis, sequenced, and analyzed using BioEdit software. A nucleotide BLAST search identified COVID-19 variants, confirmed using Cov-Lineages website.

RESULTS

In silico designed primers (S1, S2, E/M, Orf1ab) collectively exhibited 100% sensitivity in detecting SARS-CoV2 in nasopharyngeal swab samples. Individual primer sensitivities varied, with Orf1ab at 58.82% and E/M at 90.91%. Our analysis revealed the prevalence of Omicron sublineage BA.2 in the Philippines, aligning with local data showing more BA.2 cases than the global predominance of BA.1.

CONCLUSION

Combined in silico primers (S1, S2, E/M, ORF1ab) accurately detect SARS-COV-2 and its variants. This method provides a valuable diagnostic and surveillance tool for public health management.

Covid-19 ; Polymerase Chain Reaction ; Molecular Diagnostic Techniques

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, are hazardous diseases characterized by the uncontrolled proliferation of cancer cells. Dysregulated cell cycle resulting from genetic and epigenetic abnormalities constitutes one of the central events. Importantly, cyclin-dependent kinases (CDKs), complexed with their functional partner cyclins, play dominating roles in cell cycle control. Yet, efforts in translating CDK inhibitors into clinical benefits have demonstrated disappointing outcomes. Recently, mounting evidence highlights the emerging significance of WEE1 G2 checkpoint kinase (WEE1) to modulate CDK activity, and correspondingly, a variety of therapeutic inhibitors have been developed to achieve clinical benefits. Thus, WEE1 may become a promising target to modulate the abnormal cell cycle. However, its function in hematologic diseases remains poorly elucidated. In this review, focusing on hematologic malignancies, we describe the biological structure of WEE1, emphasize the latest reported function of WEE1 in the carcinogenesis, progression, as well as prognosis, and finally summarize the therapeutic strategies by targeting WEE1.
Humans ; Protein-Tyrosine Kinases/physiology* ; Hematologic Neoplasms/drug therapy* ; Cell Cycle Proteins/antagonists & inhibitors* ; Nuclear Proteins/antagonists & inhibitors* ; Cyclin-Dependent Kinases ; Molecular Targeted Therapy ; Animals

Humans ; Colorectal Neoplasms/pathology* ; Pathology, Molecular/methods* ; Biomarkers, Tumor/genetics* ; Genetic Testing ; China

Humans ; Glioma/metabolism* ; Consensus ; China ; Brain Neoplasms/pathology* ; Pathology, Molecular

Eight butyl-phthalides, senkyunolide K(1), senkyunolide N(2), butylphthalide(3), senkyunolide I(4), senkyunolide H(5),(Z)-butylidenephthalide(6),(Z)-ligustilide(7), and 3-butylidene-7-hydroxyphthalide(8) were isolated from the aerial part of Ligusticum sinense by column chromatography on silica gel column, ODS, Sephadex LH-20 and semi-preparative HPLC. Their structures were elucidated on the basis of spectroscopic and chemical data, especially NMR and MS. Compound 1 was a new butyl-phthalide and compounds 2-8 were isolated from the aerial part of L. sinense for the first time. Furthermore, the inhibitory activities of compounds 1-8 against the nitric oxide(NO) production induced by lipopolysaccharide(LPS) in mouse RAW264.7 macrophages in vitro were evaluated. The results showed that compounds 1-8 exerted inhibitory activities on NO production with IC_(50) of 19.34-42.16 μmol·L~(-1).
Animals ; Mice ; Nitric Oxide/biosynthesis* ; Ligusticum/chemistry* ; Benzofurans/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Macrophages/immunology* ; RAW 264.7 Cells ; Molecular Structure

The Baihe Dihuang Decoction(BDD) is a representative traditional Chinese medicine formula that has been used to treat depression. This study employed metabolomics and network pharmacology to investigate the mechanism of BDD in the treatment of depression. Fifty male Sprague-Dawley(SD) rats were randomly assigned to the normal control group, model group, fluoxetine group, and high-and low-dose BDD groups. A rat model of depression was established through chronic unpredictable mild stress(CUMS), and the behavioral changes were detected by forced swimming test and open field test. Metabolomics technology was used to analyze the metabolic profiles of serum and hippocampal tissue to screen differential metabolites and related metabolic pathways. Additionally, network pharmacology and molecular docking techniques were used to investigate the key targets and core active ingredients of BDD in improving metabolic abnormalities of depression. A "component-target-metabolite-pathway" regulatory network was constructed. BDD could significantly improve depressive-like behavior in CUMS rats and regulate 12 differential metabolites in serum and 27 differential metabolites in the hippocampus, involving tryptophan metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, tyrosine metabolism, and purine metabolism. Verbascoside, isorbascoside, and regaloside B were the key active ingredients for improving metabolic abnormalities in depression. Epidermal growth factor receptor(EGFR), protooncogene tyrosine-protein kinase(SRC), glycogen synthase kinase 3β(GSK3β), and androgen receptor(AR) were the key core targets for improving metabolic abnormalities of depression. This study offered a preliminary insight into the mechanism of BDD in alleviating metabolic abnormalities of depression through network regulation, providing valuable guidance for its clinical use and subsequent research.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Depression/genetics* ; Antidepressive Agents/chemistry* ; Network Pharmacology ; Hippocampus/drug effects* ; Humans ; Molecular Docking Simulation ; Behavior, Animal/drug effects* ; Disease Models, Animal

This study investigated the secondary metabolites in the product of rice fermentation with Alternaria alternata and their activity of down-regulating thymosin beta 10(TMSB10) protein expression. The secondary metabolites of A. alternata were separated and purified by various chromatographic separation techniques, including silica gel column chromatography, Sephadex LH-20 column chromatography, and semi-preparative high-performance liquid chromatography. Their structures were identified by spectral techniques such as nuclear magnetic resonance spectroscopy(NMR), infrared spectroscopy(IR), and high-resolution electrospray ionization mass spectrometry(HR-ESI-MS) and comparison with literature data. A total of 10 compounds were isolated and identified, including two new compounds(1S,3S)-2,3-dihydro-3,6-dihydroxy-8-methoxy-1-methylcyclopenta[c][2]benzopyran-5(1H)-one(1), 3,3a, 6-trihydroxy-8-methoxy-1-methyl-2,3,3a, 9b-tetrahydrocyclopenta[c]isochromen-5(1H)-one(2), and the eight known compounds are alternariol 9-methyl ether(3), 1-deoxyrubralactone(4),(3aR)-3,3a-dihydro-1,6-dihydroxy-8-methoxy-3a-methylcyclopenta[c][2]benzopyran-2,5-dione(5), altechromone A(6), alternariol(7), altenuene(8), altenusin(9), and 3'-hydroxyalternariol 5-O-methyl ether(10). The effects of these compounds on TMSB10 expression were tested. Compound 7 showed a significant down-regulation effect on TMSB10 expression with an inhibition rate of 40.5%. The results showed that benzopyrone compounds of A. alternata have the activity of down-regulating the expression of TMSB10 protein, providing theoretical basis and research value for the study of non-small cell lung cancer.
Alternaria/metabolism* ; Down-Regulation/drug effects* ; Humans ; Molecular Structure