In situ monitoring of the shikimate pathway: a combinatorial approach of Raman reverse stable isotope probing and hyperspectral imaging.

Sensing and visualization of metabolites and metabolic pathways in situ are significant requirements for tracking their spatiotemporal dynamics in a non-destructive manner. The shikimate pathway is an important cellular mechanism that leads to the de novo synthesis of many compounds containing aromatic rings of high importance such as phenylalanine, tyrosine, and tryptophan. In this work, we present a cost-effective and extraction-free method based on the principles of stable isotope-coupled Raman spectroscopy and hyperspectral Raman imaging to monitor and visualize the activity of the shikimate pathway. We also demonstrated the applicability of this approach for nascent aromatic amino acid localization and tracking turnover dynamics in both prokaryotic and eukaryotic model systems. This method can emerge as a promising tool for both qualitative and semi-quantitative in situ metabolomics, contributing to a better understanding of aromatic ring-containing metabolite dynamics across various organisms.

Excited Charge Separation in a π-Interacting Phenothiazine-Zinc Porphyrin-Fullerene Donor-Acceptor Conjugate.

We have designed, synthesized, and characterized a donor-acceptor triad, SPS-PPY-C60, that consists of a π-interacting phenothiazine-linked porphyrin as a donor and sensitizer and fullerene as an acceptor to seek charge separation upon photoexcitation. The optical absorption spectrum revealed red-shifted Soret and Q-bands of porphyrin due to charge transfer-type interactions involving the two ethynyl bridges carrying electron-rich and electron-poor substituents. The redox properties suggested that the phenothiazine-porphyrin part of the molecule is easier to oxidize and the fullerene part is easier to reduce. DFT calculations supported the redox properties wherein the electron density of the highest molecular orbital (HOMO) was distributed over the donor phenothiazine-porphyrin entity while the lowest unoccupied molecular orbital (LUMO) was distributed over the fullerene acceptor. TD-DFT studies suggested the involvement of both the S2 and S1 states in the charge transfer process. The steady-state emission spectrum, when excited either at porphyrin Soret or visible band absorption maxima, revealed quenched emission both in nonpolar and polar solvents, suggesting the occurrence of excited state events. Finally, femtosecond transient absorption spectral studies were performed to witness the charge separation by utilizing solvents of different polarities. The transient data was further analyzed by GloTarAn by fitting the data with appropriate models to describe photochemical events. From this, the average lifetime of the charge-separated state calculated was found to be 169 ps in benzonitrile, 319 ps in dichlorobenzene, 1.7 ns in toluene for Soret band excitation, and ∼320 ps for Q-band excitation in benzonitrile.

Impacts of introducing and lifting nonpharmaceutical interventions on COVID-19 daily growth rate and compliance in the United States.

We evaluate the impacts of implementing and lifting nonpharmaceutical interventions (NPIs) in US counties on the daily growth rate of COVID-19 cases and compliance, measured through the percentage of devices staying home, and evaluate whether introducing and lifting NPIs protecting selective populations is an effective strategy. We use difference-in-differences methods, leveraging on daily county-level data and exploit the staggered introduction and lifting of policies across counties over time. We also assess heterogenous impacts due to counties' population characteristics, namely ethnicity and household income. Results show that introducing NPIs led to a reduction in cases through the percentage of devices staying home. When counties lifted NPIs, they benefited from reduced mobility outside of the home during the lockdown, but only for a short period. In the long term, counties experienced diminished health and mobility gains accrued from previously implemented policies. Notably, we find heterogenous impacts due to population characteristics implying that measures can mitigate the disproportionate burden of COVID-19 on marginalized populations and find that selectively targeting populations may not be effective.

Decursin inhibits EGFR-ERK1/2 signaling axis in advanced human prostate carcinoma cells.

We have shown that decursin, a coumarin compound, induces cell cycle arrest and apoptosis in human prostate cancer cells (PCa); however, its molecular mechanisms are largely unexplored. We studied the mechanisms associated with its anticancer activity in advanced human prostate carcinoma cells. We found that decursin inhibited epidermal growth factor receptor (EGFR) signaling by inhibiting its activating phosphorylation at tyrosine 1068 residue in DU145 and 22Rv1 cells. This inhibition of EGFR was associated with the downregulation of ERK1/2 phosphorylation. Both EGFR and ERK1/2 are known to be deregulated/activated in many human malignancies. Consistent with our earlier study, decursin (25-100 µM) treatment for 24-72 h inhibited DU145 cell proliferation by 49%-87% (p < 0.001) which was associated with strong G1 phase arrest and cell death. It also decreased (p < 0.001) the number of surviving colonies. Decursin moderately increased the expression of Rb-related proteins p107 and p130 but decreased the levels of E2F family transcription factors including E2F-3, E2F-4 and E2F-5. Further, decursin strongly inhibited the growth of androgen-dependent prostate carcinoma 22Rv1 cells from 61% to 79% (p < 0.001) and arrested these cells at G1 phase via induction of cyclin-dependent kinase inhibitor p27/Kip1 and downregulation of CDK2 and CDK4 protein expression. Additionally, EGFR inhibitor erlotinib- and EGF ligand-modulated EGFR activation validated EGFR signaling as a target of decursin-mediated cell growth inhibition and cytotoxicity. Decursin decreased EGF ligand-induced phosphorylation of EGFR (Y-1068) as well as activation of its downstream mediator, ERK1/2. Furthermore, inhibitory targeting of EGFR-ERK1/2 axis by combinatorial treatment of decursin and erlotinib further sensitized DU145 cells for the decursin-induced growth inhibition and cell death. Overall, these findings strongly suggest that anticancer efficacy of decursin against human PCa involves inhibitory targeting of EGFR-ERK1/2 signaling axis, a pathway constitutively active in advanced PCa.

Fullerene C70 as Photoredox Catalyst for the Synthesis of Pyrrolo[2,1-a]isoquinolines by 1,3-Dipolar Cycloaddition-Aromatization Sequence.

Herein, fullerene (C70 ) is introduced as an effective photoredox catalyst for the construction of a highly functionalised pyrrolo[2,1-a]isoquinoline framework by 1,3-dipolar cycloaddition-aromatisation reaction sequence. The ability of C70 to efficiently harvest visible light, its long-triplet state lifetime, good photostability, and strong singlet oxygen generation potential (Φ▵ ≈1), make it an efficient photoredox catalyst. Upon photoirradiation, C70 promotes the formation of singlet oxygen and superoxide radical by energy transfer (EnT) and single electron transfer (SET) mechanism. The superoxide radical acts as a potential oxidant in the formation of azomethine ylide through the oxidation-deprotonation tandem process. Azomethine ylide further participates in [3+2]-cycloaddition reaction protocol with alkene/alkyne to give the corresponding pyrrolo[2,1-a]isoquinolines. Interestingly, this protocol allows the activation of a wide range of substrates giving access to a diverse library of 48 well-decorated pyrrolo[2,1-a]isoquinolines with good functional group tolerance.

Phenothiazine functionalized fulleropyrrolidines: synthesis, charge transport and applications to organic solar cells.

A series of phenothiazine-C60/70 dyads containing fulleropyrrolidine tethered to C-3 position (C60-PTZ and C70-PTZ) or to the heteroatom N-position via either phenyl (C60-Ph-PTZ and C70-Ph-PTZ) or phenoxyethyl linkers (C60-PhOEt-PTZ and C70-PhOEt-PTZ) of the phenothiazine were synthesized and light-induced electron transfer events were explored. Optimized studies suggested that the highest molecular orbital (HOMO) resides on donor phenothiazine moiety while lowest molecular orbital (LUMO) on the acceptor fulleropyrrolidine moiety of the dyads. Optical and electrochemical properties suggested no electronic communication between the donor and acceptor moieties in the ground state. However, steady-state emission studies in solvents of varied polarity, involving selective excitation of C60/C70, disclosed that the emission intensity of C60/C70 was quenched in the dyads in the increasing order, C60/70-PTZ > C60/70-Ph-PTZ > C60/70-PhOEt-PTZ as a consequence of the donor-acceptor distance resulted due to spacer lengths. Also, the emission quenching is more pronounced in polar solvents such as DMF compared to a non-polar solvent, toluene. With the support of parallel electrochemical studies, the emission quenching is attributed to intramolecular photo-induced electron transfer occurring from PTZ to (C60/C70)* generating a radical ion pair, PTZ+⋅-C60-⋅/PTZ+⋅-C70-⋅. Finally, bulk heterojunction (BHJ) solar cells devices inverted fashion prepared by employing the dyads as acceptors, and PTB7 as donor, suggested that the devices prepared from C70 derivatives i.e., PTB7:C70-PTZ and PTB7:C70-PhOEt-PTZ exhibited better power conversion efficiency of 2.66% and 2.15%, respectively over C60 derivatives i.e., PTB7:C60-PTZ and PTB7:C60-PhOEt-PTZ with the efficiencies of 1.80 and 1.72%, respectively. AFM studies revealed that the poor performance of PTB7:C60-PTZ- and PTB7:C60-PhOEt-PTZ-based devices can be ascribed to the lower solubility of the dyads in 1,2-DCB solvent leading to rough morphology.

Annulation of quinone methides with 2-benzylidene dithiolanes: synthesis of spirochroman dithiolanes.

An expeditious and regioselective approach towards the construction of a spiro-chroman motif is described. Quinone methides underwent a PTSA catalyzed annulation with 2-benzylidene dithiolanes to afford spiro-chroman dithiolanes in high yields. The synthetic versatility of the dithiolane motif was demonstrated by converting the adduct to coumarin, 3,4-dihydrocoumarin and chroman derivatives.

Detection of endocrine and metabolism disrupting xenobiotics in milk-derived fat samples by fluorescent protein-tagged nuclear receptors and live cell imaging.

Nuclear receptors (NRs) are ligand-modulated transcription factors that regulate multiple physiological functions in our body. Many NRs in their unliganded state are localized in the cytoplasm. The ligand-inducible nuclear translocation of NRs provides a valuable tool for studying the NR-ligand interactions and their downstream effects. The translocation response of NRs can be studied irrespective of the nature of the interacting ligand (agonist, antagonist, or a small molecule modulator). These nuclear translocation studies offer an advantage over promoter-reporter-based transcription assays where transcription response is observed only with the activating hormones or agonistic ligands. Globally, milk serves as a major dietary source. However, suspected presence of endocrine/metabolism-disrupting chemicals like bisphenols, parabens, organochlorine pesticides, carbamates, non-steroidal anti-inflammatory drugs, chloramphenicol, brominated flame retardants, etc. has been reported. Considering that these chemicals may impart serious developmental and metabolism-related health concerns, it is essential to develop assays suitable for the detection of xenobiotics present at differing levels in milk. Since milk samples cannot be used directly on cultured cells or for microscopy, a combination of screening strategies has been developed herein based on the revelation that i) lipophilic NR ligands can be successfully retrieved in milk-fat; ii) milk-fat treatment of cells is compatible with live-cell imaging studies; and finally, iii) treatment of cells with xenobiotics-spiked and normal milk derived fat provides a visual and quantifiable response of NR translocation in living cells. Utilizing a milk-fat extraction method and Green Fluorescent Protein (GFP) tagged NRs expressed in cultured mammalian cells, followed by an assessment of NR response proved to be an effective approach for screening xenobiotics present in milk samples.HighlightsDiverse endocrine and metabolism-disrupting chemicals are suspected to contaminate milk.Nuclear receptors serve as 'xenosensors' for assessing the presence of xenobiotics in milk.Nuclear import of steroid receptors with (ant)agonist can be examined in live cells.Lipophilic xenobiotics are extracted and observed enriched in milk-fat fraction.A comprehensive cell-based protocol aids in the detection of xenobiotics in milk.

Biodegradation of furfuryl alcohol by indigenous Bacillus species of industrial effluent-contaminated sites: estimation, biokinetics and toxicity assessment of bio-transformed metabolites.

Furfuryl alcohol (FA) and other furanic compounds have garnered considerable attention in the quest for sustainable alternatives. FA-based resins have been used in various sectors that entail the release of FA into the environment. Hence, to ensure sustainability in this scenario, devising a dependable approach to its degradation is imperative. Given the crucial role of bacterial strains in the biodegradation of various organic pollutants, this study investigates the microbial degradation of FA, using bacterial strains isolated from sites that are constantly exposed to industrial waste. Three potential isolates were identified as B. paramycoides, B. cereus, and B. tequilensis by 16S rRNA gene sequencing. At a concentration of 300 µg/ml, these isolates demonstrated efficient FA degradation; 60-70% (at 300 µg/ml FA) and 50-60%, (at 500 µg/ml FA). Fourier-transform infrared (FTIR) spectroscopy and High-Performance Liquid Chromatography (HPLC) analysis further supported the result that the bacterial isolates consumed FA as the carbon source. Liquid chromatography-mass spectrometry (LC-MS) facilitates the detection of the major metabolic intermediate product in which FA gets transformed. The prominent peaks at 113 and 119 m/z obtained in the MS spectra of the degraded FA samples indicated the possibility of the conversion of FA into furoic acid or levulinic acid. The phytotoxicity bioassay findings revealed the non-toxic nature of the bio-transformed products as compared to pure FA. This investigation presents the initial documentation of the FA degradative potential of Bacillus strains, thereby augmenting the understanding of the prospective implementation of Bacillus species in industrial waste treatment projects.

The WISDOM self-management intervention: A cost-effectiveness analysis to support the transformation of type 2 diabetes care in England.

OBJECTIVES: To assess the cost-effectiveness of the WISDOM self-management intervention for type 2 diabetes compared with care as usual. DESIGN: We performed a difference-in-differences analysis to estimate differences in risk factors for diabetes complications between people in the WISDOM group (n = 25, 276) and a control group (n = 15, 272) using GP records. A decision analytic model was then used to extrapolate differences in risk factors into costs and outcomes in the long term. SETTING: Participating GP practices in West Hampshire and Southampton, UK. PARTICIPANTS: All people diagnosed with type 2 diabetes between January 1990 and March 2020 (n = 40,548). OUTCOMES: Diabetes-related complications, quality-adjusted life years (QALYs) and costs to the English National Health Service at 5 years and lifetime. INTERVENTIONS: The WISDOM intervention included risk stratification, self-management education programme to professionals and people with type 2 diabetes, and monitoring of key treatment targets. RESULTS: WISDOM was associated with less atrial fibrillation [p = 0.001], albuminuria [p = 0.002] and blood pressure [p = 0.098]. Among all people in the intervention group, WISDOM led to 51 [95%CI: 25; 76] QALYs gained and saved £278,036 [95%CI: -631,900; 176,392] in the first 5 years after its implementation compared with care as usual. During those people' lifetime, WISDOM led to 253 [95%CI: 75; 404] QALYs gained and cost saving of £126,380 [95%CI: -1,466,008; 1,339,628]. The gains in QALYs were a result of reduced diabetes-related complications through improved management of the associated risk factors. CONCLUSIONS: The WISDOM risk-stratification and education intervention for type 2 diabetes appear to be cost-effective compared to usual care by reducing diabetes complications.

Neuroprotection by Mucuna pruriens in Neurodegenerative Diseases.

The medicinal plant Mucuna pruriens (Fabaceae) is widely known for its anti-oxidative and anti-inflammatory properties. It is a well-established drug in Ayurveda and has been widely used for the treatment of neurological disorders and male infertility for ages. The seeds of the plant have potent medicinal value and its extract has been tested in different models of neurodegenerative diseases, especially Parkinson's disease (PD). Apart from PD, Mucuna pruriens is now being studied in models of other nervous systems disorders such as Alzheimer's disease (AD), Amyotrophic lateral sclerosis (ALS) and stroke because of its neuroprotective importance. This review briefly discusses the pathogenesis of PD, AD, ALS and stroke. It aims to summarize the medicinal importance of Mucuna pruriens in treatment of these diseases, and put forward the potential targets where Mucuna pruriens can act for therapeutic interventions. In this review, the effect of Mucuna pruriens on ameliorating the neurodegeneration evident in PD, AD, ALS and stroke is briefly discussed. The potential targets for neuroprotection by the plant are delineated, which can be studied further to validate the hypothesis regarding the use of Mucuna pruriens for the treatment of these diseases.

Brønsted acid catalyzed annulations of ketene dithioacetals: synthesis of 3-aryl coumarins and indenes.

PTSA-catalyzed divergent synthetic routes toward 3-aryl coumarins and indenes have been developed using ketene dithioacetals. These transformations are transition-metal and oxidant free, proceed under mild conditions, and provide expeditious access to these important structural motifs.

[1]Benzothieno[3,2-b][1]benzothiophene-based dyes: effect of the ancillary moiety on mechanochromism and aggregation-induced emission.

It is an established fact that [1]benzothieno[3,2-b][1]benzothiophene (BTBT) is a champion molecule for high-mobility OFET devices. Recently, it has also been utilized in dye-sensitized solar cells (DSSCs) and organic photovoltaics (OPVs) as an alternative to fullerene (non-fullerene acceptor). Considering the advantageous features of BTBT, we herein report its aggregation-induced emission (AIE) and mechanofluorochromic (MFC) behaviour for the first time. We have designed and synthesized two new BTBT derivatives: [1]benzothieno[3,2-b][1]benzothiophene-tetraphenylethylene (BTBT-TPE) and [1]benzothieno[3,2-b][1]benzothiophene-phenyl-N,N-dimethylamine (BTBT-NMe). The donor-π-acceptor-π-donor-integrated BTBT-TPE showed AIE whereas BTBT-NMe showed aggregation-caused quenching (ACQ), as evident by their quantum yield and lifetime results. BTBT-NMe was found to possess great interaction, resulting in the halochromic (protonation) effect. The theoretical calculation of the electronic distribution and energy investigation were consistent with the experimental outcomes. The electron contribution of the HOMO is high for BTBT-NMe at the donor, which can be attributed to the weaker donating nature of TPE compared to that of the NMe group. Overall, the results indicate the potential of the mechanical stimuli and aggregation response of the studied compounds for further investigation.

Is comprehensive geriatric assessment hospital at home a cost-effective alternative to hospital admission for older people?

BACKGROUND: hospital level healthcare in the home guided by comprehensive geriatric assessment (CGA) might provide a less costly alternative to hospitalisation for older people. OBJECTIVE: to determine the cost-effectiveness of CGA admission avoidance hospital at home (HAH) compared with hospital admission. DESIGN/INTERVENTION: a cost-effectiveness study alongside a randomised trial of CGA in an admission avoidance HAH setting, compared with admission to hospital. PARTICIPANTS/SETTING: older people considered for a hospital admission in nine locations across the UK were randomised using a 2:1 randomisation schedule to admission avoidance HAH with CGA (N = 700), or admission to hospital with CGA when available (N = 355). MEASUREMENTS: quality adjusted life years, resource use and costs at baseline and 6 months; incremental cost-effectiveness ratios were calculated. The main analysis used complete cases. RESULTS: adjusting for baseline covariates, HAH was less costly than admission to hospital from a health and social care perspective (mean -£2,265, 95% CI: -4,279 to -252), and remained less costly with the addition of informal care costs (mean difference -£2,840, 95% CI: -5,495 to -185). There was no difference in quality adjusted survival. Using multiple imputation for missing data, the mean difference in health and social care costs widened to -£2,458 (95% CI: -4,977 to 61) and societal costs remained significantly lower (-£3,083, 95% CI: -5,880 to -287). There was little change to quality adjusted survival. CONCLUSIONS: CGA HAH is a cost-effective alternative to admission to hospital for selected older people.

The MreA Metal-Binding Sites C40, H65, and C69 Play a Critical Role in the Metal Tolerance of Pseudomonas putida KT2440.

Metal-binding proteins occur in the cytosol of most eubacteria. The hypothetical metal responsive protein MreA (PP-2969 gene; NreA) seems responsible for zinc, chromium, cadmium accumulation, and metal ion homeostasis. However, there is a lack of definitive evidence regarding the specific metal-binding sites of MreA protein. The present study aimed to identify putative metal-binding regions for MreA. In silico analysis revealed that amino acids C40, H65, and C69 (CHC region) seem critical for metal-protein interactions. We created site-directed mutants (SDM's) of MreA for interacted amino acids to validate in silico results. The differential scanning fluorimetry (DSF) and atomic absorption spectroscopy (AAS) showed that SDM strains of MreA protein curtailed metal accumulation compared to the wild types indicating C40, H65, and C69 amino acids are critical for metal binding. Thus, we report potential implications for MreA-bioengineered strains of Pseudomonas putida KT2440 for metal ion homeostasis by alleviating metal toxicity in the biological environment.

Factors influencing the adsorption of antibiotics onto activated carbon in aqueous media.

Widespread use of antibiotics for treating human and animal ailments has increased their discharge in the environment through excreta. Moreover, unscientific disposal of unused antibiotics has further increased their presence in the environmental matrices. Thus, occurrence of used and/or discarded antibiotics in water resources is becoming a growing concern across the globe. Antibiotics and their residues in the aquatic environment are emerging contaminants which pose a serious threat to the aquatic biota as well as human beings by enhancing antibiotic resistance. Various methods are being adopted for the removal of these contaminants. Adsorption over activated carbon is one such promising method which is environmentally friendly, cost-effective, and efficient. However, there are various factors which affect the overall process efficiency, such as, properties of activated carbon/antibiotics/reaction medium etc. In this article, emphasis has been laid down on evaluating these factors, so that the experimental procedures may be optimized to obtain the highest possible removal efficiency for antibiotics in the aqueous media.

Global footprints of organochlorine pesticides: a pan-global survey.

Organochlorine pesticides (OCPs) are ubiquitous environmental contaminants widely used all over the world. These chlorinated hydrocarbons are toxic and often cause detrimental health effects because of their long shelf life and bioaccumulation in the adipose tissues of primates. OCP exposure to humans occurs through skin, inhalation and contaminated foods including milk and dairy products, whereas developing fetus and neonates are exposed through placental transfer and lactation, respectively. In 1960s, OCPs were banned in most developed countries, but because they are cheap and easily available, they are still widely used in most third world countries. The overuse or misuse of OCPs has been rising continuously which pose threats to environmental and human health. This review reports the comparative occurrence of OCPs in human and bovine milk samples around the globe and portrays the negative impacts encountered through the long history of OCP use.

Sorption of pharmaceuticals over microplastics' surfaces: interaction mechanisms and governing factors.

Microplastics are one of the emerging and ubiquitous environmental pollutants. Recent studies have proven their co-existence with pharmaceuticals in the environment wherein microplastics act as a potential vector for the transportation of pharmaceuticals. Both microplastics and pharmaceuticals are charged moieties enriched with diverse functional groups resulting in the possibility of multiple interactions. Major interactions could be electrostatic, hydrogen bonding, and hydrophobic, while minor interactions may occur through π-π interaction, cationic bridging mechanism, van der Waals interaction, partition, and pore-filling mechanism. These interactions have both short- and long-term effects over pharmaceutical sorption on microplastics and possibly, ensuing toxicity. This review analyses and summarises the currently reported interactions between microplastic particles and pharmaceuticals as well as establishes the link to various factors affecting the process, viz. pH, salinity, dissolved organic matter, and physiochemical properties of microplastics.

Pluripotency of embryonic stem cells lacking clathrin-mediated endocytosis cannot be rescued by restoring cellular stiffness.

Mouse embryonic stem cells (mESCs) display unique mechanical properties, including low cellular stiffness in contrast to differentiated cells, which are stiffer. We have previously shown that mESCs lacking the clathrin heavy chain (Cltc), an essential component for clathrin-mediated endocytosis (CME), display a loss of pluripotency and an enhanced expression of differentiation markers. However, it is not known whether physical properties such as cellular stiffness also change upon loss of Cltc, similar to what is seen in differentiated cells, and if so, how these altered properties specifically impact pluripotency. Using atomic force microscopy (AFM), we demonstrate that mESCs lacking Cltc display higher Young's modulus, indicative of greater cellular stiffness, compared with WT mESCs. The increase in stiffness was accompanied by the presence of actin stress fibers and accumulation of the inactive, phosphorylated, actin-binding protein cofilin. Treatment of Cltc knockdown mESCs with actin polymerization inhibitors resulted in a decrease in the Young's modulus to values similar to those obtained with WT mESCs. However, a rescue in the expression profile of pluripotency factors was not obtained. Additionally, whereas WT mouse embryonic fibroblasts could be reprogrammed to a state of pluripotency, this was inhibited in the absence of Cltc. This indicates that the presence of active CME is essential for the pluripotency of embryonic stem cells. Additionally, whereas physical properties may serve as a simple readout of the cellular state, they may not always faithfully recapitulate the underlying molecular fate.

Pathophysiology linking depression and type 2 diabetes: Psychotherapy, physical exercise, and fecal microbiome transplantation as damage control.

Diabetes increases the likelihood of developing depression and vice versa. Research on this bidirectional association has somewhat managed to delineate the interplay among implicated physiological processes. Still, further exploration is required in this context. This review addresses the comorbidity by investigating suspected common pathophysiological mechanisms. One such factor is psychological stress which disturbs the hypothalamic-pituitary-adrenal axis causing hormonal imbalance. This includes elevated cortisol levels, a common biomarker of both depression and diabetes. Disrupted insulin signaling drives the hampered neurotransmission of serotonin, dopamine, and norepinephrine. Also, adipokine hormones such as adiponectin, leptin, and resistin and the orexigenic hormone, ghrelin, are involved in both depression and T2DM. This disarray further interferes with physiological processes encompassing sleep, the gut-brain axis, metabolism, and mood stability. Behavioral coping mechanisms, such as unhealthy eating, mediate disturbed glucose homeostasis, and neuroinflammation. This is intricately linked to oxidative stress, redox imbalance, and mitochondrial dysfunction. However, interventions such as psychotherapy, physical exercise, fecal microbiota transplantation, and insulin-sensitizing agents can help to manage the distressing condition. The possibility of glucagon-like peptide 1 possessing a therapeutic role has also been discussed. Nonetheless, there stands an urgent need for unraveling new correlating targets and biological markers for efficient treatment.