Unveiling the full spectrum of maitake mushrooms: A comprehensive review of their medicinal, therapeutic, nutraceutical, and cosmetic potential.

This literature review provides an up-to-date exploration of the multifaceted attributes of maitake mushrooms (Grifola frondosa), elucidating their bioactive phytochemicals and diverse health advantages, including their substantial role in supporting human health and potential incorporation into the medicinal industry. Carbohydrates and protein are the major constituents contributing to the dry weight of G. frondosa, taking up around 70-80 % and 13-21 %, respectively, with emerging research linking these constituents to various health benefits. By synthesising current research findings, this review emphasises the substantial role of maitake mushrooms in supporting human health and underscores their potential incorporation into the medicinal industry. To further advance our understanding, future research should delve into the mechanisms underlying their health-promoting effects, with a focus on conducting quantitative studies to elucidate physiological pathways and potential drug interactions. Additionally, exploring their integration into functional foods or nutraceuticals through quantitative assessments of bioavailability and efficacy will be crucial for maximising their therapeutic benefits. This review aims to provide comprehensive insights, catalysing further research and innovation in utilising maitake mushrooms for improved well-being and industry advancement.

Co-factor independent oxidases ncnN and actVA-3 are involved in the dimerization of benzoisochromanequinone antibiotics in naphthocyclinone and actinorhodin biosynthesis.

Streptomyces produce complex bioactive secondary metabolites with remarkable chemical diversity. Benzoisochromanequinone polyketides actinorhodin and naphthocyclinone are formed through dimerization of half-molecules via single or double carbon-carbon bonds, respectively. Here we sequenced the genome of S. arenae DSM40737 to identify the naphthocyclinone gene cluster and established heterologous production in S. albus J1074 by utilizing direct cluster capture techniques. Comparative sequence analysis uncovered ncnN and ncnM gene products as putative enzymes responsible for dimerization. Inactivation of ncnN that is homologous to atypical co-factor independent oxidases resulted in the accumulation of fogacin, which is likely a reduced shunt product of the true substrate for naphthocyclinone dimerization. In agreement, inactivation of the homologous actVA-3 in S. coelicolor M145 also led to significantly reduced production of actinorhodin. Previous work has identified the NAD(P)H-dependent reductase ActVA-4 as the key enzyme in actinorhodin dimerization, but surprisingly inactivation of the homologous ncnM did not abolish naphthocyclinone formation and the mutation may have been complemented by an endogenous gene product. Our data suggests that dimerization of benzoisochromanequinone polyketides require two-component reductase-oxidase systems.

Drug reaction with eosinophilia and systemic symptoms syndrome secondary to isoniazid and ethambutol: a case report and literature review.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe, potentially life-threatening condition precipitated by reaction of therapeutic drugs. The prevalence of potential antitubercular therapy (ATT)-induced DRESS is 1.2%. Case presentation: A 71-year-old female patient after 5 weeks of starting ATT complaints of fever, vomiting, dizziness, and generalized itchy maculopapular rash over the body. It was associated with marked eosinophilia (absolute eosinophil count 3094 cell/mm3, 36% in peripheral blood smear). Discussion: Fever, rash, lymphadenopathy, and internal organ involvement with marked eosinophilia constitute the major clinical manifestations of DRESS. RegiSCAR scoring system is usually used to diagnose DRESS. Identification of the culprit drug is based on the temporal correlation of symptoms with drug exposure and rechallenge test, patch test and lymphocytic transformation tests may be valuable adjunctive tools. Treatment includes withdrawal of offending agent and use of topical or systemic corticosteroids, antihistamines, cyclosporin or JAK inhibitor with clinical judgement. Conclusion: Clinicians from the tuberculosis burden region must be aware of DRESS associated with ATT and they must counsel the patient properly before prescription and manage them without delay if DRESS ensues.

The Phytochemistry of Ganoderma Species and their Medicinal Potentials.

The Ganoderma genus is known for its diverse use as a functional food and therapeutic agent. This fungus has over 428 species, with Ganoderma lucidum being the most studied. The Ganoderma species produce several secondary metabolites and bioactive compounds like polysaccharides, phenols, and triterpenes, which are largely responsible for their therapeutic properties. Throughout this review, several extracts obtained from Ganoderma species have been studied to delve into their therapeutic characteristics and mechanisms. Such properties like immunomodulation, antiaging, antimicrobial, and anticancer activities have been demonstrated by several Ganoderma species and are supported by a large body of evidence. Although its phytochemicals play a vital role in its therapeutic properties, identifying the therapeutic potentials of fungal-secreted metabolites for human health-promoting benefits is a challenging task. Identification of novel compounds with distinct chemical scaffolds and their mechanism of action could help suppress the spread of rising pathogens. Thus, this review provides an updated and comprehensive overview of the bioactive components in different Ganoderma species and the underlying physiological mechanisms.

Phages against killer superbugs: An enticing strategy against antibiotics-resistant pathogens.

The emerging resistivity of antibiotic resistance superbugs desire the need to resolve the global problem of antibiotic resistance. Among several other methods currently being adopted, one possible solution may be the development of supplemental therapies for antibiotics. The use of the normal and advanced bactericidal properties of bacteriophages (bacteriophage therapy) may be one of the viable infection control options. It is evident, however, that the safe and regulated application of phage treatment will need extensive knowledge of the characteristics and behaviour of certain phage-bacterium systems. This mini review offers an overview of the potential for phage therapy as well as the constraints and obstacles it faces in becoming a commonly accepted infection management strategy.

Single cell mutant selection for metabolic engineering of actinomycetes.

Actinomycetes are important producers of pharmaceuticals and industrial enzymes. However, wild type strains require laborious development prior to industrial usage. Here we present a generally applicable reporter-guided metabolic engineering tool based on random mutagenesis, selective pressure, and single-cell sorting. We developed fluorescence-activated cell sorting (FACS) methodology capable of reproducibly identifying high-performing individual cells from a mutant population directly from liquid cultures. Actinomycetes are an important source of catabolic enzymes, where product yields determine industrial viability. We demonstrate 5-fold yield improvement with an industrial cholesterol oxidase ChoD producer Streptomyces lavendulae to 20.4 U g-1 in three rounds. Strain development is traditionally followed by production medium optimization, which is a time-consuming multi-parameter problem that may require hard to source ingredients. Ultra-high throughput screening allowed us to circumvent medium optimization and we identified high ChoD yield production strains directly from mutant libraries grown under preset culture conditions. Genome-mining based drug discovery is a promising source of bioactive compounds, which is complicated by the observation that target metabolic pathways may be silent under laboratory conditions. We demonstrate our technology for drug discovery by activating a silent mutaxanthene metabolic pathway in Amycolatopsis. We apply the method for industrial strain development and increase mutaxanthene yields 9-fold to 99 mg l-1 in a second round of mutant selection. In summary, the ability to screen tens of millions of mutants in a single cell format offers broad applicability for metabolic engineering of actinomycetes for activation of silent metabolic pathways and to increase yields of proteins and natural products.

Bioprospecting the Metabolome of Plant Urtica dioica L.: A Fast Dereplication and Annotation Workflow in Plant Metabolomics.

Plants have a pivotal role in ethnopharmacology, and their preparations are in use globally. However, getting down to the structure requires an effective workflow and mostly requires a time-consuming isolation process. Although bioassay-guided approaches are widely popular, they face a massive problem of rediscovery in recent times, especially in plant metabolomics. Mass spectrometry (MS)-based approach incorporated molecular networking via Global Natural Product Social Molecular Networking (GNPS) is considered here for the benefit of the fast screening of secondary metabolites. This study uses direct crude extracts obtained from various parts of the Urtica dioica plant for the characterization of secondary metabolites. The crude extract of the plant initially displayed promising antioxidant and anti-diabetic activities. Then, we employed mass spectrometry-based dereplication to identify the phytochemical components in the extracts. This led to the discovery of 7 unknown and 17 known secondary metabolites, which were further verified with the SIRIUS 4 platform, a computational tool for the annotation of compounds using tandem MS data. On the other hand, chasing the antioxidant activity of methanolic extract of U. dioica leaves, we employed a bioassay-guided isolation approach. With this method, we isolated and characterized compound 13, a known molecule, which possessed strong antioxidant activity without showing much toxicity in the brine shrimp lethality test at the test concentration of 1 mg/mL. With our results, we advocate the MS-based approach as a good starting point for the dereplication of compounds from the complex crude extracts of plants.

Therapeutic drug level of tacrolimus causing intracranial hemorrhage in a patient with renal transplant.

Tacrolimus is used in solid organ transplant patients to prevent rejection, and no case of intracerebral hemorrhage (ICH) has been reported till date. We report a case of 31-year-old man with diabetes and hypertension for ten years who had a renal transplant four years back; diagnosed with tacrolimus-induced ICH.

Ethnomedicinal landscape: distribution of used medicinal plant species in Nepal.

BACKGROUND: The risk of losing traditional knowledge of medicinal plants and their use and conservation is very high. Documenting knowledge on distribution and use of medicinal plants by different ethnic groups and at spatial scale on a single platform is important from a conservation planning and management perspective. The sustainable use, continuous practice, and safeguarding of traditional knowledge are essential. Communication of such knowledge among scientists and policy makers at local and global level is equally important, as the available information at present is limited and scattered in Nepal. METHODS: In this paper, we aimed to address these shortcomings by cataloguing medicinal plants used by indigenous ethnic groups in Nepal through a systematic review of over 275 pertinent publications published between 1975 and July 2021. The review was complemented by field visits made in 21 districts. We determined the ethnomedicinal plants hotspots across the country and depicted them in heatmaps. RESULTS: The heatmaps show spatial hotspots and sites of poor ethnomedicinal plant use documentation, which is useful for evaluating the interaction of geographical and ethnobotanical variables. Mid-hills and mountainous areas of Nepal hold the highest number of medicinal plant species in use, which could be possibly associated with the presence of higher human population and diverse ethnic groups in these areas. CONCLUSION: Given the increasing concern about losing medicinal plants due to changing ecological, social, and climatic conditions, the results of this paper may be important for better understanding of how medicinal plants in use are distributed across the country and often linked to specific ethnic groups.

Reactivation of herpes zoster after vaccination with an inactivated vaccine: A case report from Nepal.

COVID-19 has been linked to a number of cutaneous symptoms in COVID-19 patients. Although herpes zoster (HZ) was the first sign of COVID-19 infection in several patients, cases of HZ after COVID-19 vaccination are rare. Here, we report a case of 51-year-old male patient with herpes zoster after Sinopharm (Vero cell) vaccination.

Next-generation microbial drugs developed from microbiome's natural products.

Scientists working in natural products chemistry have been enticed by the current advancements being made in the discovery of novel "magic bullets" from microbes homed to all conceivable environments. Even though researchers continue to face challenges funneling the novel bioactive compounds in the global therapeutic industries, it seems most likely that the discovery of some "hit molecules" with significant biomedical applications is not that far. We applaud novel natural products for their ability to combat the spread of superbugs and aid in the prevention of currently observed antibiotic resistance. This in-depth investigation covers a wide range of microbiomes with a proclivity for synthesizing novel compounds to combat the spread of superbugs. Furthermore, we use this opportunity to explore various groups of secondary metabolites and their biosynthetic pathways in various microbiota found in mammals, insects, and humans. This systematic study, when taken as a whole, offers detail understanding on the biomedical fate of various groups of compounds originated from diverse microbiomes. For gathering all information that has been uncovered and released so far, we have also presented the huge diversity of microbes that are associated with humans and their metabolic products. To conclude, this concrete review suggests novel ideas that will prove immensely helpful in reducing the danger posed by superbugs while also improving the efficacy of antibiotics.

Retroperitoneal Fibrosis as a presentation with masked multiorgan involvement of IgG4-related disease-demystifying the diagnosis: A case report from Nepal.

The timely diagnosis of the disease helps in preventing the progression of RF and unnecessary interventions that may mislead the diagnosis. Biopsy and serum IgG4 both can be non-specific.

A Patient Infected with SARS-CoV-2 Presenting with Complete Heart Block.

Complete heart block is a rare presentation in a patient with COVID-19 infection that may result when the virus enters the myocardial cell by the angiotensin-converting enzyme-2 receptor. Here, we report a case of forty-nine-year male with COVID-19 with complete heart block (CHB).

Maculosin, a non-toxic antioxidant compound isolated from Streptomyces sp. KTM18.

CONTEXT: Streptomyces species are prolific sources of bioactive secondary metabolites known especially for their antimicrobial and anticancer activities. OBJECTIVE: This study sought to isolate and characterize antioxidant molecules biosynthesized by Streptomyces sp. KTM18. The antioxidant potential of an isolated compound and its toxicity were accessed. MATERIALS AND METHODS: The compound was purified using bioassay-guided chromatography techniques. Nuclear magnetic resonance (NMR) experiments were carried out for structure elucidation. The antioxidant potential of the isolated compound was determined using DPPH free radical scavenging assay. The toxicity of the isolated compound was measured using a brine shrimp lethality (BSL) assay. RESULTS: Ethyl acetate extract of Streptomyces sp. KTM18 showed more than 90% inhibition of DPPH free radical at 50 µg/mL of the test concentration. These data were the strongest among 13 Streptomyces isolates (KTM12-KTM24). The active molecule was isolated and characterized as maculosin (molecular formula, C14H16N2O3 as determined by the [M + H]+ peak at 261.1259). The DPPH free radical scavenging activity of pure maculosin was higher (IC50, 2.16 ± 0.05 µg/mL) than that of commercial butylated hydroxyanisole (BHA) (IC50, 4.8 ± 0.05 µg/mL). No toxicity was observed for maculosin (LD50, <128 µg/mL) in brine shrimp lethality assay (BSLA) up to the compound's antioxidant activity (IC50) concentration range. The commercial standard, berberine chloride, showed toxicity in BSLA with an LD50 value of 8.63 ± 0.15 µg/mL. CONCLUSIONS: Maculosin may be a leading drug candidate in various cosmetic and therapeutic applications owing to its strong antioxidant and non-toxic properties.

Fungal natural products galaxy: Biochemistry and molecular genetics toward blockbuster drugs discovery.

Secondary metabolites synthesized by fungi have become a precious source of inspiration for the design of novel drugs. Indeed, fungi are prolific producers of fascinating, diverse, structurally complex, and low-molecular-mass natural products with high therapeutic leads, such as novel antimicrobial compounds, anticancer compounds, immunosuppressive agents, among others. Given that these microorganisms possess the extraordinary capacity to secrete diverse chemical scaffolds, they have been highly exploited by the giant pharma companies to generate small molecules. This has been made possible because the isolation of metabolites from fungal natural sources is feasible and surpasses the organic synthesis of compounds, which otherwise remains a significant bottleneck in the drug discovery process. Here in this comprehensive review, we have discussed recent studies on different fungi (pathogenic, non-pathogenic, commensal, and endophytic/symbiotic) from different habitats (terrestrial and marines), the specialized metabolites they biosynthesize, and the drugs derived from these specialized metabolites. Moreover, we have unveiled the logic behind the biosynthesis of vital chemical scaffolds, such as NRPS, PKS, PKS-NRPS hybrid, RiPPS, terpenoids, indole alkaloids, and their genetic mechanisms. Besides, we have provided a glimpse of the concept behind mycotoxins, virulence factor, and host immune response based on fungal infections.

Probing phenylcarbamoylazinane-1,2,4-triazole amides derivatives as lipoxygenase inhibitors along with cytotoxic, ADME and molecular docking studies.

Hunting small molecules as anti-inflammatory agents/drugs is an expanding and successful approach to treat several inflammatory diseases such as cancer, asthma, arthritis, and psoriasis. Besides other methods, inflammatory diseases can be treated by lipoxygenase inhibitors, which have a profound influence on the development and progression of inflammation. In the present study, a series of new N-alkyl/aralky/aryl derivatives (7a-o) of 2-(4-phenyl-5-(1-phenylcarbamoyl)piperidine-4H-1,2,4-triazol-3-ylthio)acetamide was synthesized and screened for their inhibitory potential against the enzyme 15-lipoxygenase. The simple precursor ethyl piperidine-4-carboxylate (a) was successively converted into phenylcarbamoyl derivative (1), hydrazide (2), semicarbazide (3) and N-phenylated 5-(1-phenylcarbamoyl)piperidine-1,2,4-triazole (4), then in combination with electrophiles (6a-o) through further multistep synthesis, final products (7a-o) were generated. All the synthesized compounds were characterized by FTIR, 1H, 13C NMR spectroscopy, EIMS, and HREIMS spectrometry. Almost all the synthesized compounds showed excellent inhibitory potential against the tested enzyme. Compounds 7c, 7f, 7d, and 7g displayed potent inhibitory potential (IC50 9.25 ± 0.26 to 21.82 ± 0.35 µM), followed by the compounds 7n, 7h, 7e, 7a, 7b, 7l, and 7o with IC50 values in the range of 24.56 ± 0.45 to 46.91 ± 0.57 µM. Compounds 7c, 7f, 7d exhibited 71.5 to 83.5% cellular viability by MTT assay compared with standard curcumin (76.9%) when assayed at 0.125 mM concentration. In silico ADME studies supported the drug-likeness of most of the molecules. In vitro inhibition studies were substantiated by molecular docking wherein the phenyl group attached to the triazole ring was making a π-δ interaction with Leu607. This work reveals the possibility of a synthetic approach of compounds in relation to lipoxygenase inhibition as potential lead compounds in drug discovery.

Strategic Moves of "Superbugs" Against Available Chemical Scaffolds: Signaling, Regulation, and Challenges.

Superbugs' resistivity against available natural products has become an alarming global threat, causing a rapid deterioration in public health and claiming tens of thousands of lives yearly. Although the rapid discovery of small molecules from plant and microbial origin with enhanced bioactivity has provided us with some hope, a rapid hike in the resistivity of superbugs has proven to be the biggest therapeutic hurdle of all times. Moreover, several distinct mechanisms endowed by these notorious superbugs make them immune to these antibiotics subsequently causing our antibiotic wardrobe to be obsolete. In this unfortunate situation, though the time frame for discovering novel "hit molecules" down the line remains largely unknown, our small hope and untiring efforts injected in hunting novel chemical scaffolds with unique molecular targets using high-throughput technologies may safeguard us against these life-threatening challenges to some extent. Amid this crisis, the current comprehensive review highlights the present status of knowledge, our search for bacteria Achilles' heel, distinct molecular signaling that an opportunistic pathogen bestows to trespass the toxicity of antibiotics, and facile strategies and appealing therapeutic targets of novel drugs. Herein, we also discuss multidimensional strategies to combat antimicrobial resistance.

Antibiotic drug discovery: Challenges and perspectives in the light of emerging antibiotic resistance.

Amid a rising threat of antimicrobial resistance in a global scenario, our huge investments and high-throughput technologies injected for rejuvenating the key therapeutic scaffolds to suppress these rising superbugs has been diminishing severely. This has grasped world-wide attention, with increased consideration being given to the discovery of new chemical entities. Research has now proven that the relatively tiny and simpler microbes possess enhanced capability of generating novel and diverse chemical constituents with huge therapeutic leads. The usage of these beneficial organisms could help in producing new chemical scaffolds that govern the power to suppress the spread of obnoxious superbugs. Here in this review, we have explicitly focused on several appealing strategies employed for the generation of new chemical scaffolds. Also, efforts on providing novel insights on some of the unresolved questions in the production of metabolites, metabolic profiling and also the serendipity of getting "hit molecules" have been rigorously discussed. However, we are highly aware that biosynthetic pathway of different classes of secondary metabolites and their biosynthetic route is a vast topic, thus we have avoided discussion on this topic.

Genotyping-Guided Discovery of Persiamycin A From Sponge-Associated Halophilic Streptomonospora sp. PA3.

Microbial natural products have been a cornerstone of the pharmaceutical industry, but the supply of novel bioactive secondary metabolites has diminished due to extensive exploration of the most easily accessible sources, namely terrestrial Streptomyces species. The Persian Gulf is a unique habitat for marine sponges, which contain diverse communities of microorganisms including marine Actinobacteria. These exotic ecosystems may cradle rare actinomycetes with high potential to produce novel secondary metabolites. In this study, we harvested 12 different species of sponges from two locations in the Persian Gulf and isolated 45 symbiotic actinomycetes to assess their biodiversity and sponge-microbe relationships. The isolates were classified into Nocardiopsis (24 isolates), Streptomyces (17 isolates) and rare genera (4 isolates) by 16S rRNA sequencing. Antibiotic activity tests revealed that culture extracts from half of the isolates displayed growth inhibitory effects against seven pathogenic bacteria. Next, we identified five strains with the genetic potential to produce aromatic polyketides by genotyping ketosynthase genes responsible for synthesis of carbon scaffolds. The combined data led us to focus on Streptomonospora sp. PA3, since the genus has rarely been examined for its capacity to produce secondary metabolites. Analysis of culture extracts led to the discovery of a new bioactive aromatic polyketide denoted persiamycin A and 1-hydroxy-4-methoxy-2-naphthoic acid. The genome harbored seven gene clusters involved in secondary metabolism, including a tetracenomycin-type polyketide synthase pathway likely involved in persiamycin formation. The work demonstrates the use of multivariate data and underexplored ecological niches to guide the drug discovery process for antibiotics and anticancer agents.

Spinal Anaesthesia for Laparoscopic Cholecystectomy in Parkinson's Disease.

Parkinson's disease, a neurodegenerative disorder, presents with resting tremor, muscle rigidity and bradykinesia. Affecting multiple organ-systems, it's an important cause of peri-operative morbidity. General anaesthesia may deteriorate cardio-pulmonary and neuro-cognitive functions; moreover, medications used may interact with anti-parkinsonian agents. Spinal anaesthesia is usually avoided in Parkinson's disease. However, it offers neurologic monitoring and less surgical stress response and avoids complications of general anaesthesia. This case report aims to demonstrate application of spinal anaesthesia for laparoscopic cholecystectomy in a Parkinson's elderly with pulmonary dysfunction and anticipated difficult airway management. Sensory blockade of third thoracic dermatome was achieved. Bupivacaine was instilled intra-peritoneally. Surgery was smooth at low intra-abdominal pressure. Regular Paracetamol provided satisfactory post-operative analgesia. Single episode of post-operative vomiting was effectively managed. Without deterioration, patient was discharged from hospital on third day. Spinal anaesthesia is a valid technique for laparoscopic cholecystectomy in needy patients with multiple peri-operative risks. Keywords: Laparoscopic cholecystectomy; Parkinson's disease; spinal anaesthesia.