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ABSTRACTIntroductionCancer cells adopt a glycolytic phenotype to fulfill their energy needs in unfavorable conditions. In metabolic rewiring, cancer cells upregulate the expression of glycolytic pathway regulators including glucose transporter 1, hexokinase 2, and PKM2 (pyruvate kinase) into its M2 splice form. Among these regulators, PKM2 plays a major role in metabolic reprogramming and is overexpressed in various diseases, including cancer. Dimerization of PKM2 causes the generation of synthetic precursors from glycolytic intermediates, which are essential for cellular growth and cancer cell proliferation.Covered areasThis article is focused on examining recent patents (2018–2023) on PKM2 activators, inhibitors and their biological and synthesis properties by using the advanced search service of the European Patent Office (EPO). Moreover, other databases including PubMed, Google Scholar and Elsevier were also examined for scientific data. On basis of their chemical structures, PKM2 activators and inhibitors are classified into pyrazole, pyrolidine-pyrazole, phenol, benzoxazine, isoselenazolo-pyridinium, phthalazine, and propiolylamide derivatives.Expert OpinionActivating PKM2 reduces proliferation and development of cells by reducing the quantity of biomolecules needed for cell formation. PKM2 activators and inhibitors are highly effective in treating many cancer pathogens. It is important to find new, more potent and selective molecules for PKM2 activation and inhibition.

Synergistic chemo-photothermal therapy is employed to treat cancer. In this work, the curcumin loaded mesoporous silica on reduced graphene oxide (Cur-mSiO2@rGO) is synthesized. The mSiO2@rGO nanocarrier combines rGO to absorb NIR radiations with mSiO2to load the drug. The mSiO2@rGO thus functions as bimodal photothermal agent and pH-responsive drug nanocarrier. Curcumin loaded onto the nanocarrier possesses antiproliferative, antioxidant, anti-inflammatory, pro-apoptotic, and antiangiogenic characteristics. It has anticancer potential against malignancies of stomach, liver, breast, lungs, and prostate. Breast cancer (BCa) is a major health concern worldwide. Curcumin inhibits BCa by mechanisms including apoptosis, cell cycle arrest, and modulation of signaling pathways. Moreover, curcumin blocks transcription factor (NF-κB), PI3K/AKT signaling, and STAT3 protein to inhibit liver cancer cell growth and survival. Cur-mSiO2@rGO targets cancer cells with enhanced loading capacity of 92 ± 1.02 % curcumin which is specifically released in the acidic tumor environment. NIR lamp irradiation at 808 nm ablates cancer cells to demonstrate the high photothermal conversion efficiency of rGO. In vitroexperiments prove that synergistic chemo-photothermal therapy effectively kills cancer cells (HepG2 and MCF-7) compared to the single chemotherapeutic treatment. The toxicity of Cur-mSiO2@rGO is analyzed in vivoby the serum biochemical analysis, and biosafety by histopathological examination of vital body organs. A 1000 mg/kg specific dose of Cur-mSiO2@rGO shows no toxic effect on mice organs. Additionally, the in vivostudies confirm that Cur-mSiO2@rGO with NIR reduces tumor growth. Therefore, the multifunctional Cur-mSiO2@rGO can be a safe chemopreventive nanocarrier in tumor management and cancer photothermal therapy.

Neurodegeneration is a multifactorial process involved the different cytotoxic pathways that lead to neuronal cell death. Alzheimer’s disease (AD) is a persistent neurodegenerative disorder that normally has a steady onset and gradually worsens. Neuropathology, AD is characterized by the presence of neuroinflammation, mitochondrial dysfunction, increased oxidative stress, decreased antioxidant defense as well as increased acetylcholinesterase activity. Moreover, enhanced expression of amyloid precursor proteins leads to neural apoptosis, which has a vital role in the degeneration of neurons. The inability of commercial therapeutics to treat a single feature of AD pathology leads to the attraction towards organic drugs. Ellagic acid is a dimer of gallic acid; latest studies revealed that ellagic acid can initiate numerous cell signaling transmissions and decrease the progression of neurodegeneration. The neuroprotective effects of ellagic acid to protect the neurons against neurodegenerative events are due to its antioxidant effect, iron chelating, and mitochondrial protective effect. The main goal of this review is to critically analyze the molecular mechanism of action of ellagic acid against AD.

Natural products have served as a limitless reservoir of bioactive scaffolds for drug discovery against several disorders. Furanodiene is a bioactive natural product isolated from several plants of genus Curcuma. Its therapeutic potential against cancer, inflammation, and angiogenesis has been well-documented. The current review is an update about the natural sources and anti-cancer action mechanism of furanodiene. Furanodiene exerts its anti-cancer effects via induction of apoptosis in several cancer types by modulating MAPKs/ERK, NF-ΚB, and Akt pathways. Furanodiene has been systematically studied for its anti-cancer potential. However, pharmacokinetics, pharmacodynamics, pre-clinical and clinical studies still needed to be conducted to completely validate the potential of furanodiene for the treatment of cancer.

Nature has provided prodigious reservoirs of pharmacologically active compounds for drug development since times. Physcion and physcion 8-O-β-D-glucopyranoside (PG) are bioactive natural anthraquinones which exert anti-inflammatory and anticancer properties with minimum or no adverse effects. Moreover, physcion also exhibits anti-microbial and hepatoprotective properties, while PG is known to have anti-sepsis as well as ameliorative activities against dementia. This review aims to highlight the natural sources and anticancer activities of physcion and PG, along with associated mechanisms of actions. On the basis of the literature, physcion and PG regulate multitudinous cell signaling pathways through the modulation of various regulators of cell cycle, protein kinases, microRNAs, transcriptional factors, and apoptosis linked proteins resulting in the effective killing of cancerous cells in vitro as well as in vivo. Both compounds effectively suppress metastasis, furthermore, physcion acts as an inhibitor of 6PGD and also plays an important role in chemosensitization. This review article suggests that physcion and PG are potent anticancer drug candidates, but further investigations on their mechanism of action and pre-clinical trials are mandatory in order to comprehend the full potential of these natural cancer killers in anticancer remedies.

Nature always remains an inexhaustible source of treasures for mankind. It remains a mystery for every challenge until the completion of the challenge. While we talk about the complicated health issues, nature offers us a great variety of chemical scaffolds and their various moieties packed in the form of natural products e.g., plants, microorganisms (fungi, algae, protozoa), and terrestrial vertebrates and invertebrates. This review article is an update about jaceosidin, a bioactive flavone, from genus Artemisia. This potentially active compound exhibits a variety of pharmacological activities including anti-inflammatory, anti-oxidant, anti-bacterial, antiallergic and anti-cancer activities. The bioactivities and the therapeutic action of jaceosidin, especially the modulation of different cell signaling pathways (ERK1/2, NF-ΚB, PI3K/Akt and ATM-Chk1/2) which become deregulated in various pathological disorders, have been focused here. The reported data suggest that the bioavailability of this anti-cancer compound should be enhanced by utilizing various chemical, biological and computational techniques. Moreover, it is recommended that researchers and scientists should work on exploring the mode of action of this particular flavone to precede it further as a potent anti-cancer compound.

•Non-genetic factors shape cancer evolution and influence therapeutic outcomes.•Non-genetic heterogeneity diverse subpopulations of cancer cells within breast tumors, can arise through clonal evolution, genetic changes, epigenetic changes, and reversible phenotypic transitions.•Intratumoral heterogeneity revealed by immunological microenvironment has opened novel opportunities for immunotherapy research.•This review focus on adaptive methods; alterations in drug targets, immune system evasion, activation of survival pathways, and alterations in metabolism.

Termites are important pest of crops, trees, and household wooden installments. Two species Coptotermes heimiand Heterotermes indicolaare the major species of termites that results in great economic loss in Asia including Pakistan. Chitinases have drawn interest because of their relevance as biological control of pests. The study was performed to screen chitinolytic bacteria from dead termites and to determine their chitinolytic activity in degrading chitin content of termites. Ten isolates were obtained forming clear zones on chitin-containing agar plates. One isolate (JF66) had the highest (3.3 mm) chitinolytic index. Based on sequence of 16S rRNA gene, the isolate was identified as Stenotrophomonas maltophiliawith (99%) similarity under Accession number KC849451 (JF66), and DNA G + C content was found to be (54.17%). S. maltophilia(JF66) produces chitinases upto 1757.41 U/ml at 30 °C and pH 6.0 employing diammonium phosphate as a nitrogen source. Chitinase gene was also extracted and gets sequenced that confirmed its presence. Whole culture and different concentrations of crude enzyme of the isolate were tested on the chitin covering of termites. Mortalities showed that crude enzyme of isolate could degrade chitin of both species of the termites C. heimiand H. indicola. Chitinase produced by S. maltophiliahad potential application as biocontrol agent for termites, but it is assumed that purification of chitinases may produce more prominent results.

The synthesis of novel acefyllines and exploring their biological activities attract researchers due to their medicinal applications. Therefore, the current work reports the successful synthesis of a series of novel acefyllines in good yields, and their structures wereconfirmed using various spectroscopic methods. The synthesized acefyllines demonstrated moderate activity (cell viability = 22.55 ± 0.95% − 57.63 ± 3.65%) compared with the starting drug acefylline (cell viability = 80 ± 3.87%) against the human liver carcinoma (Hep G2 cell line). N-(4-Chlorophenyl)-2-(4-(3,4-dichlorophenyl)-5-((1,3-dimethyl-2,6-dioxo-2,3-dihydro-1H-purin-7(6H)-yl)methyl)-4H-1,2,4-triazol-3-ylthio)acetamide exhibited the most potent activity (cell viability = 22.55 ± 0.95%) among the synthesized derivatives. The in silico modeling studies were performed to predict the binding of the most potent derivative with a binding site that agreed with the results of the antiproliferative activity. The newly synthesized heterocycles exhibited the least hemolytic and moderate clot lysis activity.

Probiotics are living micro-organism preparations which can vigorously inhibit the probable pathogens colonization in the gut microbial ecology. Current experiment was designed to investigate the efficacy of imported probiotic species compared with the indigenous probiotics species on the oxidative stress, enzymes, and hormones in animal model. Thirty Albino rats were equally divided into three groups with 10 rats (n= 10) in each group as Control (C), supplemented with imported probiotic species (IP), and supplemented with indigenous probiotics species (InP) for 21 days under controlled environment. The evaluation of treatments was done by testing the serum oxidative stress markers, liver enzymes (Aspartate transaminase and Alanine aminotransferase), lipid profile, and hormonal dynamics including Lutinizing hormone (LH), follicular stimulating hormone (FSH), and growth hormone (GH) in albino male rats. Results revealed that use of indigenous probiotic species significantly (p< 0.05) reduces the oxidative stress and improves the antioxidant capacity; liver enzymes, total cholesterol, and LDL-Cholesterol were also reduced significantly (p< 0.05) in InP as compared to IP group. Moreover, results of hormones including LH, FSH, and GH explored that indigenous probiotics have significant (p< 0.05) potential to improve these hormones as compared to imported probiotics. Although, it could be concluded that InP have beneficial role in preventing the body from oxidative stress as well as in improving the blood parameters but comprehensive studies are required to investigate the detail gut ecology of the indigenous species which will definitely a strong support in preparing a more suitable local probiotic supplement.

Stress caused due to examinations during any degree program and at any educational level has been observed at all levels so the present study was conducted to investigate the stress related to final examination in undergraduate students with reference to their academic performance. Fifty-four volunteers were divided into three groups, (n= 18), according to their academic performance, that is, Group A with low CGPA (⩽2.99), Group B with average CGPA (⩾3.00–3.59) and Group C with high CGPA (⩾3.60) and blood samples (3 ml) were taken at three-time intervals, that is, pre-examination, during examination and post examination time interval, at the Department of Physiology, Government College University, Faisalabad. Anthropometric parameters like height, weight, blood pressure, heart rate and body mass index (BMI) were also determined. Blood cortisol and thyroid hormones (triiodothyronine, T3; thyroxine, T4) and thyroid stimulating hormone (TSH)) were measured using ELISA based technique. Arylesterase activity (ARE) and paraoxonase activity (PON-1) were also measured using colorimetric method. The results showed that overall cortisol level was increased at pre-examination and during examination time intervals as compared to the post examination time interval while PON-1 and ARE were significantly (p< 0.05) decreased. With regards to T4 and TSH, a non-significant (p< 0.05) difference was observed in pre and post examination time interval. It could be concluded from the current study that semester system examinations significantly (p< 0.05) imposed stress in all students group at pre-examination interval as compare to post examination interval and this examination related stress was find more in the students already obtained low CGPA as compared to the other studied groups. Although, a correlation between academic performance and examinations stress in semester system was found but a large scale trial in multiple institutions throughout the Pakistan is required to exclude any socioeconomic factors because Pakistan belongs to developing country.

Natural products, a rich source of bioactive chemical compounds, have served humans as a safer drug of choice since times. Eriocalyxin B, an ent-Kaurene diterpenoid, has been extracted from a traditional Chinese herb Isodon eriocalyx. Experimental data support the anticancer and anti-inflammatory activities of EriB. This natural entity exhibits anticancer effects against breast, pancreatic, leukemia, ovarian, lung, bladder, and colorectal cancer. EriB has capability to inhibit the proliferation of cancer cells by prompting apoptosis, arresting cell cycle, and modulating cell signaling pathways. The regulation of signaling pathways in cancerous cells by EriB involves the modulation of various apoptosis-related factors (Bak, Bax, caspases, XIAP, survivin, and Beclin-1), transcriptional factors (nuclear factor kappa B [NF-κB], STAT3, Janus-activated kinase 2, Notch, AP-1, and lκBα), enzymes (cyclooxygenase 2, matrix metalloproteinase 2 [MMP-2], MMP-9, and poly (ADP-ribose) polymerase), cytokines, and protein kinases (mitogen-activated protein kinase and ERK1/2). This review proposes that EriB supplies a novel opportunity for the cure of cancer but supplementary investigations along with preclinical trials are obligatory to effectively figure out its biological and pharmacological applications.

Nature, an expert craftsman of molecules, has generated extensive array of bioactive molecular entities. It persists as an inexhaustible resource for discovery of drugs and supplied enormous scaffold diversification for development into effectual drugs to treat multiple pathological conditions. This review provides an update on the sources, biological, and pharmacological effects of nature's gift, a triterpenoid saponin, tubeimoside-1 which is a major bioactive constituent of the bulb of Bolbostemma paniculatum. Tubeimoside-1 is known to possess various pharmacological properties such as anti-cancer, anti-HIV, and anti-inflammatory. Recently, anti-proliferative potential of tubeimoside-1 has been widely studied. The present review article seeks to cover the recent developments of tubeimoside-1′s pharmacological position in the arena of herbal drugs, providing an insight into its current status in therapeutic pursuits. This anti-cancer triterpenoid saponin fight cancer progression by induction of apoptosis, cell cycle arrest, and inhibiting metastasis by specifically targeting multiple signaling pathways those are usually deregulated in various cancers. The reported data recommend tubeimoside-1′s mutitarget activity in preference to single effect that may perform an imperative role towards developing tubeimoside-1 into potential pharmacological drug.